Publications
2026
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Polygenic risk for schizophrenia predicting age-specific fluctuations in depressive symptoms: Findings from the Young Finns Study
CONCLUSIONS: First, PRSscz appears to explain age-specific fluctuations in depressive symptoms. Second, PRSscz may not predict the full symptom profile of major depression (i.e., it was not associated with affective/somatic symptoms). Third, high PRSscz explains depressive symptoms during periods typical for prodromal syndromes, even among those who do not develop psychosis. Thus, depressive symptoms in adolescence may represent intermediary phenotypes or transdiagnostic susceptibilities related... -
Assessing Behavioral and Environmental Facets of Obesity Unobtrusively Utilizing Digital Tools: Introducing the BETTER4U Indicators
Understanding obesity involves evaluating numerous contributing factors. Collecting the necessary data for this can impose a significant burden on both research participants during clinical studies and real-life deployments of digital tools aiding obesity management. The BETTER4U project (European Union's Horizon Europe, Grant Agreement ID 101080117) introduces 36 behavioral and 9 living environment indicators designed to unobtrusively and efficiently capture daily life through passive... -
Lipoprotein(a): Particle vs mass and prevalent cardiovascular disease in the cardiovascular risk in Young Finns study population
CONCLUSION: Molar and mass showed comparable associations with cardiovascular outcomes. However, molar reporting aligned more closely with the genetic and structural determinants of Lp(a) and more often assigned individuals to higher guideline-based risk categories, supporting continued standardization toward particle-based reporting. -
The growing burden of myopia in Europe: evidence from population-based cohorts
Myopia is a childhood-onset condition driven by excessive axial ocular elongation, associated with increased risk of sight-threatening complications and irreversible visual impairment. Despite rising global prevalence, epidemiological data on long-term trends in Europe remain limited. This study examines temporal trends in myopia prevalence and axial length (AL) across European adult birth cohorts. We conducted a comparative birth-cohort analysis using harmonised data from 28 population-based... -
Which Behavior Change Techniques Are Consistently Used in Effective Obesity-Related Interventions for Vulnerable Populations? A Meta-Review
CONCLUSION: The results provide insights into behavior change techniques that may be prioritized in interventions aimed at weight reduction among adults from vulnerable populations. -
Effects of Polygenic Risk Scores and Physical Activity on Blood Pressure Trajectories in Childhood, Adolescence, and Young Adulthood
CONCLUSIONS: Our study suggests that genetic influences on BP are evident as early as age 5 and extend to dynamic changes in SBP during puberty and DBP during postpuberty. Higher physical activity may reduce SBP levels in puberty independent of genetic susceptibility. -
Author Correction: Obesity rise plateaus in developed nations and accelerates in developing nations
No abstract -
Robust inference and correlates from genetic associations with personality
Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments^(1,2). Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14 million participants with European-like and African-like... -
Ultrasound-detected fatty liver in young adults and long-term risk of atherosclerotic cardiovascular disease: The Young Finns Study
CONCLUSIONS: Fatty liver in young adults was associated with incident CHD after adjustment for atherogenic dyslipidaemia and systemic inflammation, with modest attenuation after adjustment for insulin resistance. The association with composite CVD was substantially attenuated after adjustment for apoB. These findings support fatty liver as a marker of later CVD risk in young adults. -
Adolescent weight gain trajectories and their associations with biological aging: a genetically informed study
CONCLUSIONS: Our findings indicate that high BMI in adolescence may accelerate biological aging, especially in individuals with a genetic predisposition to high BMI. Adolescents with a genetic susceptibility to high BMI and elevated BMI might be prone to obesity-related health risks, highlighting early prevention strategies' importance. -
Early life and adulthood risk factors for middle age P-wave prolongation and left atrial enlargement
CONCLUSION: Excess BMI from childhood through adulthood is a key determinant of atrial remodelling in middle age. These findings highlight the long-term impact of early life adiposity and underscore the importance of lifelong weight management in preventing atrial cardiomyopathy and its clinical sequelae. -
Temporal stability of cardiometabolic risk factors from the perspective of primordial disease prevention in children
CONCLUSIONS: Individualised biomarker screening at low FPR misclassifies the majority of children who will have high values as adults (low statistical feasibility). Biomarker tracking is more useful for guiding broad population-based primordial prevention programmes that can be extended to all children at risk without harm from false positives. -
The length of the embryo culture in assisted reproductive technology does not have a major impact on newborn DNA methylation
Blastocyst culture is an essential part of IVF/ICSI treatments, however, it has been shown to increase the risk of preterm deliveries as well as large for gestational age infants. The effect of the extended culture on offspring phenotype is thought to be mediated by epigenetic mechanisms, since this developmental period coincides with extensive epigenetic remodelling. Here, we compare genome-wide DNA methylation of cord blood and umbilical cord artery samples collected from newborns resulting... -
Genetic architecture and cross-platform validation of apolipoprotein A-IV concentrations
CONCLUSION: These results provide a comprehensive overview of the genetic architecture of apoA-IV and suggest mechanistic links to lipid metabolism, kidney function and blood-related traits. Our findings refine the role of apoA-IV as a potential biomarker and inform future epidemiological research. -
Ceramide-Phospholipid Risk Score Associates With Cardiovascular Events and Is Lowered by Atorvastatin, Simvastatin, and Anti-PCSK9 Treatments
CONCLUSIONS: The CERT2 risk score is a significant predictor of cardiovascular outcomes in all-comer patients with symptomatic or suspected coronary heart disease. Treatment with lipid-lowering medication significantly lowers the CERT2 risk score. -
Traditional Disease Risk Factors Outperform Epigenetic Clocks as Predictors of Non-Communicable Disease Morbidity in a Middle-Aged Cohort
DNA methylation-based epigenetic clocks have been highlighted as promising biomarkers of ageing, and they have been shown to robustly predict morbidity and mortality. However, current literature is lacking a formal analysis of the increased prediction accuracy, or the added value, of the epigenetic clocks over traditional risk factors, such as body composition, smoking, or alcohol consumption, in predicting common chronic diseases. Here, we have compared the most commonly used epigenetic clocks... -
The case for primary prevention of obesity in the era of GLP-1 therapies
Obesity rates continue to rise across Europe, driven by obesogenic environments shaped by food systems, urban design, socioeconomic inequalities, and commercial forces. The introduction of incretin-based pharmacotherapies like GLP-1 receptor agonists has transformed treatment, leading to significant weight loss and metabolic benefits for many. This progress has shifted public and policy discourse, with some suggesting that effective treatment reduces the urgency of prevention. However, this... -
The associations of childhood and adolescence psychosocial risks with social relations in midlife
We examined whether the accumulation of psychosocial risk factors (socioeconomic risks, health behavioural risks, stressful life-events and psycho-emotional risks) in childhood and adolescence contributes to insufficient social relations (loneliness, frequency and heterogeneity of social contacts and social support) in adulthood participants from the longitudinal Young Finns Study with a 38-year follow-up (N = 1787, 56% female). Results from regression models indicated that a higher cumulative... -
Earliest age to detect lifetime cardiometabolic health stratification in children
CONCLUSIONS: Adult-like cardiometabolic stratification is detectable in young children, but accuracy (without extreme indication) may be too low for personalized risk prediction. Consequently, we emphasize broad preventative programs that extend into adulthood to reduce the overall prevalence of cardiometabolic risk factors in the population. -
Role of resilience in modifying the links between genetic propensity for mental disorders and irritability
CONCLUSIONS: Polygenic liabilities for affective disorders but not schizophrenia are associated with higher irritability trajectories between ages 20 and 50 years. Individuals with higher or lower PRSs appeared to benefit from early resilience indices in a largely similar manner, except for school career and leisure time activities, which seemed to have particularly strong protective effects in individuals with high PRSs. -
Whole blood epigenomic and transcriptomic characterization identifies vulnerable molecular subtypes of chronic coronary disease
Chronic coronary disease (CCD) remains a leading cause of morbidity and mortality worldwide. However, current clinical assessments, including tests of inducible ischemia or coronary artery disease severity poorly discriminate risk for future cardiovascular (CV) disease events among this population with established CCD. To address this gap, our study leverages high-dimensional molecular data from the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive... -
Obesity rise plateaus in developed nations and accelerates in developing nations
Global reporting of obesity is commonly based on comparisons over multiple decades¹ and lacks a granular and systematic analysis of its dynamics. We used 4,050 population-based studies with measured height and weight data on 232 million participants to assess the worldwide dynamics of obesity from 1980 to 2024. The rise in obesity decelerated in school-aged children and adolescents throughout the 1990s in many high-income countries, and subsequently plateaued in most at age-standardized... -
Physical Activity Since Childhood and its Association with Changes in Midlife Cognitive Functions: A Longitudinal Prospective Cohort Study
CONCLUSIONS: The results suggest that individuals with higher life-course PA experience a smaller decrease in executive aspects of cognitive function during midlife. -
Uncovering the similarities of lipidome-wide markers of carotid artery plaque and metabolic dysfunction-associated fatty liver disease: the Young Finns study
Metabolic dysfunction-associated fatty liver disease (MAFLD) and carotid artery plaque (CAP) are both linked to circulatory lipid and lipoprotein metabolism. However, the shared lipidome-wide mechanisms underlying these diseases remain unexplored. To identify plasma lipid species associated with both MAFLD and CAP to uncover their shared metabolic pathways. We analyzed data from the Young Finns Study cohort from the 2007 and 2018 follow-ups (n = 1496, aged 41-56 years, 56.3% females). Ultrasound... -
<em>Trans</em>-eQTLs reveal the architecture of human gene regulatory networks
Many non-coding variants influence complex traits and diseases through gene regulation, yet the mechanisms linking these variants to downstream biology remain poorly understood. Here, we present eQTLGen Phase 2, a comprehensive genome-wide analysis of gene expression quantitative trait loci (eQTLs) in 43,301 blood samples from 52 datasets. Beyond local ciseffects, this sample size enabled the first systematic mapping of trans-eQTLs at scale. We identify cis-eQTLs for nearly all expressed genes... -
Therapeutic TG2 inhibition reverses systemic multiomic dysregulation in celiac disease
BACKGROUND: Celiac disease (CeD) is an autoimmune disease triggered by dietary gluten in genetically predisposed individuals. Deamidation of gluten peptides by the CeD autoantigen and enzyme transglutaminase 2 (TG2) is central to the pathogenesis of CeD. Inhibition of TG2 with the specific inhibitor ZED1227 effectively prevents gluten-induced histological damage in CeD patients. Here we aimed to explore the systemic plasma lipidomic, proteomic and DNA methylomic changes in ZED1227-treated CeD... -
Nature's Curriculum: Genes Linked to Educational Attainment and Adult Socioeconomic Status Across Birth Cohorts in a Nordic Welfare State
Recent research has identified genes linked to educational attainment, but their effects on subsequent socioeconomic outcomes, particularly in egalitarian Nordic welfare states, remain largely unexplored. We analyze two genetically informed Finnish datasets, encompassing longitudinal register information on earnings, employment, unemployment, occupational status, and social assistance receipt (n = 31,622). We examine the role of a polygenic score for educational attainment (EA PGS), achieved... -
Diet Quality, Physical Activity, and Epigenetic Aging in the Finnish Working-Age Population
CONCLUSIONS: Healthier eating over the follow-up was associated with decelerated epigenetic changes across different diet indices. In terms of biological aging, having a healthy diet may be especially crucial for those with low levels of physical activity. -
Are There Any Effective Behavior Change Strategies for Communicating Genetic Risk in Obesity Prevention and Body Weight Reduction Interventions?
This systematic review examined how differences in intervention components may contribute to inconsistent findings in genetic risk communication studies, addressing obesity-related outcomes (e.g., weight reduction, nutrition behavior, exercise). The review was preregistered (PROSPERO #CRD42024524026) and followed PRISMA guidelines. Searches across eight databases identified 23 randomized controlled trials, covering 18 intervention trials. Risk of bias was assessed using the Risk of Bias 2 tool.... -
Discovery of gene-alcohol interaction loci influencing blood pressure in 1.1 million individuals from multiple populations
Genetic predisposition and alcohol consumption are risk factors for increased blood pressure (BP), but their interactions influencing BP remain understudied. We conducted population-specific and cross-population meta-analyses of genome-wide gene-alcohol (GxAlc) interactions affecting BP in >1.1M individuals from multiple populations. We identified 46 GxAlc interaction loci for BP, including 21 from one-degree-of-freedom interaction tests (PGxAlc<5×10-8; or <0.05/Meff, Meff independent BP... -
Longitudinal association of circulating inflammatory biomarkers with epigenetic ageing in the Young Finns Study
DNA methylation-based epigenetic clocks are reliable measures of biological age and aging rate. Chronic inflammation may contribute to aging and various diseases, but population-based studies on specific inflammatory biomarkers’ impact on epigenetic clocks are limited. The aim of this study was to investigate the associations between 38 circulating inflammatory biomarkers, as well as a combined systemic inflammation variable, and epigenetic clocks in a middle-aged population. The cohort included... -
Deleterious coding variation associated with autism is shared across ancestries
The past decade has seen remarkable progress in identifying genes that, when impacted by deleterious coding variation, confer high likelihood for autism spectrum disorder (ASD), intellectual disability and other associated developmental disorders. However, most underlying gene discovery efforts have focused on individuals of European ancestry, limiting insights into genetic liability across diverse populations. To help address this, the Genomics of Autism in Latin American Ancestries (GALA)... -
Prognostic implications of intraventricular conduction disorders for the risk of sudden cardiac death in cardiac patients
CONCLUSION: NIVCD and prolonged QRS are strong predictors of SCD events despite adjusting for risk factors including LVEF. -
Gene-by-Sleep Duration Interaction for Glycemic Traits in over 480,000 Individuals
Both short and long sleep duration have been associated with poor glycemic control and an increased risk of developing type 2 diabetes mellitus. Although sleep duration may differentially modify the effects of genetic risk factors for type 2 diabetes, this has not been systematically investigated. In the present study, we conducted genome-wide gene by sleep duration meta-analyses, separately assessing interactions of short and long sleep, for fasting glucose, fasting insulin, and hemoglobin A1c... -
Prognostic potential of circulatory miR-19a-3p, miR-19b-3p, and miR-329-3p for future hypertension diagnosis
MicroRNAs have been suggested as essential hypertension biomarkers, but evidence remains inconclusive due to limited high-throughput studies in population cohorts. We analyzed data from the Young Finns Study (YFS) from 2011 and 2018-2020 to assess cross-sectional and prospective associations between circulatory microRNAs, blood pressure (BP), and hypertension. Hypertension risk prediction potential was assessed using nested logistic and Weibull survival models; model performance was evaluated... -
Meta-analysis of genome-wide association studies of food allergy and IgE sensitization
CONCLUSION: This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies. -
EpiSmokEr2: a robust epigenetic classifier for smoking status inference using Illumina EPIC methylation data
CONCLUSION: EpiSmokEr2 provides a reliable DNAm-based estimator of smoking status. It is available as an open-source R package on GitHub, facilitating broad use in epidemiological and clinical research. -
Neighbourhood socioeconomic disadvantage from childhood to midlife and carotid atherosclerosis
CONCLUSIONS: Long-term exposure to neighbourhood socioeconomic disadvantage beginning in childhood is associated with subclinical atherosclerosis in midlife, independently of achieved socioeconomic position. These findings highlight the importance of cumulative socioeconomic environments across the life course and suggest that behavioural risk factors may partly explain observed neighbourhood-level associations with atherosclerosis. -
A genome-wide association meta-analysis of cholesterol synthesis intermediates identifies three associations for lanosterol
BACKGROUND: Cholesterol is a main contributor to coronary artery disease (CAD). Although the genetic basis of blood cholesterol concentration is well studied, there is currently a lack of studies investigating the genetics of its precursors from de novo biosynthesis. -
Polygenic risk for schizophrenia predicting test-measured and self-reported cognitive performance in individuals without psychosis
CONCLUSION: We observed lower cognitive functioning in domains similar to those reported in studies of patients with schizophrenia. Thus, some difficulties in cognitive performance may not be fully attributable to the disorder itself but may partly reflect normative developmental trajectories in individuals with high polygenic liabilities. -
Large-scale blood pressure GWAS accounting for gene-depression interactions in 564,680 individuals from diverse populations
Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci... -
Multi-modal choroid plexus pathology in aging and Alzheimer's disease
Brain barriers, cerebrospinal fluid (CSF) dynamics, and peripheral factors are implicated as significant contributors to Alzheimer's disease (AD). The choroid plexus (ChP) is a blood-brain interface that produces CSF and forms the blood-CSF barrier. However, how ChP pathology develops across the lifespan and contributes to AD has not been systematically characterized. Here, we report a multi-modal ChP atlas integrating single-nucleus transcriptomics from 49 individuals, AI-assisted quantitative... -
Cohort Profile Update: Expanding the Cardiovascular Risk in Young Finns Study into a multigenerational cohort
No abstract -
Genome-wide DNA methylation patterns for indicators of liver steatosis: a longitudinal multiomic study
CONCLUSIONS: Our findings highlight the association between the methylation levels of cg06690548 (SLC7A11) and liver steatosis, describe the dynamic relationship between whole blood DNA methylation and MASLD, and contribute to a deeper understanding of the pathophysiology of liver diseases. -
Life-Course Blood Pressure Levels, 38-Year Tracking, and Prediction of Hypertension
CONCLUSIONS: These data indicate that long-term cumulative exposure to elevated BP levels in childhood/adolescence are associated with a substantially increased risk of adult hypertension. -
Differential effects of adolescent health behaviours on adult cardiometabolic health by parental and neighbourhood socioeconomic background
Adolescent healthy behaviours may improve cardiometabolic health in adulthood differently across socioeconomic groups. We aimed to quantify the effects of adolescent healthy behaviours on multiple biomarkers of adult cardiometabolic health by socioeconomic backgrounds. We used a population-based cohort of Finnish adolescents from the Young Finns Study (1980-89, n = 2984) followed into adulthood (2001-11). Healthy behaviours (no smoking, no alcohol consumption, sufficient physical activity, daily... -
Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure
CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden. -
Association of epicardial adipose tissue thickness and cardiac structure and function in early midlife: the cardiovascular risk in Young Finns Study
CONCLUSION: Our results suggest associations between EAT thickness, increased LV wall thickness, LA size, and decreased mitral annular velocity in early adulthood. The observed alterations in these specific cardiac metrics are particularly known as early structural alterations linked with obesity-related LV concentric remodelling and relaxation abnormalities. Thus, EAT may contribute in cardiac subclinical remodelling initiating in early adulthood, which may lead to various cardiovascular... -
Diagnosing migraine from genome-wide genotype data: a machine learning analysis
Migraine has an assumed polygenic basis, but the genetic risk variants identified in genome-wide association studies only explain a proportion of the heritability. We aimed to develop machine learning models, capturing non-additive and interactive effects, to address the missing heritability. This was a cross-sectional population-based study of participants in the second and third Trøndelag Health Study. Individuals underwent genome-wide genotyping and were phenotyped based on validated modified...
2025
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Large-Scale Gene-Smoking Interactions and Fine Mapping Study Identifies Multiple Novel Blood Pressure Loci in over 1 Million Individuals
Cigarette smoking influences blood pressure (BP) levels. Studying and accounting for potential gene-smoking interactions can help discover novel loci and provide insights into biological pathways for smoking-associated BP regulation. We conducted a genome-wide association meta-analysis involving 1,188,241 individuals from 66 studies in five ancestry groups, analyzing systolic BP, diastolic BP, and pulse pressure while considering interactions between genetic variants and three smoking exposures:... -
Life-Course Blood Pressure Levels, 38-Year Tracking, and Prediction of Hypertension
CONCLUSIONS: These data indicate that long-term cumulative exposure to elevated BP levels in childhood/adolescence are associated with a substantially increased risk of adult hypertension. -
Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure
CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden. -
Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database
Incomplete penetrance, or absence of disease phenotype in an individual with a disease-associated variant, is a major challenge in variant interpretation. Studying individuals with apparent incomplete penetrance can shed light on underlying drivers of altered phenotype penetrance. Here, we investigate clinically relevant variants from ClinVar in 807,162 individuals from the Genome Aggregation Database (gnomAD), demonstrating improved representation in gnomAD version 4. We then conduct a... -
A multilayer network analysis of cardiovascular-depression comorbidity reveals symptom-specific molecular biomarkers
CONCLUSIONS: This network-based analysis revealed symptom-specific biological pathways linking CVD and depression. The identified biomarkers may offer insights into shared mechanisms and support future prevention and treatment strategies for cardiometabolic-psychiatric comorbidity. -
Meta-analyses of clozapine, norclozapine levels and their ratio across three genome wide association studies
Recent genome wide association studies (GWAS) found associations between clozapine serum levels and single nucleotide polymorphisms (SNP) in intragenic region between cytochrome P450 1A1 (CYP1A1) and CYP1A2 and nuclear factor 1B (NFIB). The aim of this study was to perform another GWAS of polymorphisms associated with the serum levels of clozapine and norclozapine, their ratios, and to perform meta-analyses with two previous GWAS. Finnish clozapine patients (n = 170) with known smoking habits... -
Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus
Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed trans expression quantitative trait locus (trans-eQTL) meta-analysis in 3734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset of 682 individuals. The trans-eQTL signal at the ubiquitin specific... -
The effect of polychlorinated biphenyls on type 2 diabetes risk is mediated via DNA methylation
Polychlorinated biphenyls (PCBs) have been identified as diabetogens and potential epigenetic regulators. Epigenetic variation is implicated in the pathogenesis of type 2 diabetes (T2D) and is therefore a potential mechanism linking PCB exposure and T2D. We here investigate the effect of PCB exposure on T2D risk and the extent to which this is mediated via DNA methylation (DNAm) using two epigenome-wide association studies and mediation analysis. Exposure to PCBs, especially congeners 74, 99,... -
Electrocardiogram markers predicting ischemic stroke after acute coronary syndrome
CONCLUSIONS: ECG markers demonstrating LV dysfunction, LVH and atriopathy associate with IS risk after ACS, although external validation is still required. -
Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques
CONCLUSIONS: Latent chronic bacterial inflammation evades immune detection and may contribute to the pathogenesis of complicated atherosclerotic plaques and fatal myocardial infarction. -
Polygenic prediction of body mass index and obesity through the life course and across ancestries
Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European... -
Prevalence of carotid atherosclerosis in 3-92-year-old Finns. The 3-generational cardiovascular risk in young Finns study
CONCLUSIONS: Carotid artery plaques are very prevalent finding among Finnish adults but not observed in children of the general population. High LDL-cholesterol concentration and hypertension are strongly associated with plaques, especially among young adults. On the other hand, these data demonstrate that a substantially large proportion of young and middle-aged adults with plaques cannot be identified by the assessment of conventional risk factors. -
Life-course neighbourhood socioeconomic disadvantage and atherosclerotic carotid artery plaques. The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Long-term exposure to neighbourhood socioeconomic disadvantage beginning in childhood is associated with subclinical atherosclerosis in midlife independently of achieved socioeconomic position. Behavioural risk factors partially mediate this link, highlighting the importance of early and sustained interventions targeting both social environments and health behaviours to mitigate cardiovascular risk. -
Factors related to blood-based biomarkers for neurodegenerative diseases and their intergenerational associations in the Young Finns Study: a cohort study
BACKGROUND: Blood-based biomarkers (BBM) of neurodegenerative diseases are emerging as cost-effective tools in the differential diagnostics of Alzheimer's disease and other dementias. Scarce data exist about factors explaining BBM variation in population-based cohorts, and their intergenerational associations are unknown. This study aimed to characterise BBM distributions among a population-based cohort, investigate the association of a wide array of factors with BBM both in midlife and old age,... -
A phenome-wide association study of genetically determined nicotine metabolism reveals novel links with health-related outcomes
Faster nicotine metabolism, defined as the nicotine metabolite ratio (NMR), is known to associate with heavier smoking and challenges in smoking cessation. However, the broader health implications of genetically determined nicotine metabolism are not well characterized. We performed a hypothesis-free phenome-wide association study (PheWAS) of over 21,000 outcome variables from UK Biobank (UKB) to explore how the NMR (measured as the 3-hydroxycotinine-to-cotinine ratio) associates with the... -
The associations between intergenerational mobility of income and cognitive function in midlife-The Young Finns Study
CONCLUSIONS: Individuals with stable high income may have better midlife cognitive function. This finding highlights the role of life-course SES for disparities in adulthood cognitive function. Understanding the role of early-life determinants of midlife cognitive function is important, as this knowledge may be applied to the early promotion of adulthood cognitive health. -
MR-link-2: pleiotropy robust cis Mendelian randomization validated in three independent reference datasets of causality
Mendelian randomization (MR) identifies causal relationships from observational data but has increased Type 1 error rates (T1E) when genetic instruments are limited to a single associated region, a typical scenario for molecular exposures. We developed MR-link-2, which leverages summary statistics and linkage disequilibrium (LD) to estimate causal effects and pleiotropy in a single region. We compare MR-link-2 to other cis MR methods: i) In simulations, MR-link-2 has calibrated T1E and high... -
Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids
Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of... -
Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality
Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family... -
Polygenic risk for schizophrenia predicting Big Five personality traits in individuals without non-affective psychosis
CONCLUSIONS: Individuals with high PRS for schizophrenia, who have not developed non-affective psychosis, may still develop mildly different personality traits, including higher Openness and lower Extraversion. These findings seem to be specific to PRSscz and are not observed for PRS(DEP). -
Tracking and Trajectory Analysis of Active Commuting from Childhood to Midlife
CONCLUSIONS: Tracking of AC from childhood to mid-adulthood was low to moderately high. Stable and increasing AC trajectories predicted higher adult PA levels during weekdays or weekends. -
Morbidity-bridging metabolic pathways: linking early cardiovascular disease risk and depression symptoms using a multi-modal approach
CONCLUSION: This study integrated three statistical techniques and identified two metabolic markers (glucose, omega-3 FAs) connecting depression and CVD on a symptom and risk factor level. The associations, established in a relatively young cohort, were replicated in a predominantly middle-aged cohort and emphasize both the generalizability of the findings across different populations and value of symptom-level analysis in depression and CVD comorbidity research. -
Polygenic risk for schizophrenia and subjective well-being in a general population sample
CONCLUSIONS: While high PRS(SCZ) has been linked to multiple adversities in previous studies, we did not find any association between high PRS(SCZ) and subjective measures of life satisfaction, optimism, and self-acceptance. -
Regulation of nc886 (vtRNA2-1) RNAs is associated with cardiometabolic risk factors and diseases
Non-coding 886 (nc886, vtRNA2-1) is a polymorphically imprinted gene. The methylation status of this locus has been shown to be associated with periconceptional conditions, and both the methylation status and the levels of nc886 RNAs have been shown to associate with later-life health traits. We have previously shown that nc886 RNA levels are associated not only with the methylation status of the locus, but also with a genetic polymorphism upstream from the locus. In this study, we describe the... -
A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations
Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration... -
Sleep disturbances, shift work, and epigenetic ageing in working-age adults: findings from the Young Finns study
CONCLUSIONS: Among various sleep measures, symptoms of obstructive sleep apnoea appear to be most consistently associated with accelerated epigenetic ageing even after adjusting for various health-related and socioeconomic factors. Shift work seems to have a crucial role in the relationship between sleep disturbances and epigenetic ageing in working-age adults. -
Correction to "Personalized Profiling of Lipoprotein and Lipid Metabolism Based on 1018 Measures from Combined Quantitative NMR and LC-MS/MS Platforms"
No abstract -
Metabolic transition from childhood to adulthood based on two decades of biochemical time series in three longitudinal cohorts
CONCLUSION: Novel associations between emerging cardiometabolic risk factors, such as amino acids and glycoprotein acetyls, and growth and puberty were observed. Conversely, apolipoprotein B was stable, which favors its utility for early assessments of lifetime cardiovascular risk. -
Blood pressure in childhood, young- and mid-adulthood: association with carotid plaque severity
CONCLUSIONS: Blood pressure at each life stage contributes equally to carotid plaque presence, with mid-adulthood BP associated with a greater contribution to plaque area. These findings underscore the importance of maintaining normal BP throughout life to reduce atherosclerosis risk and suggest that intensive BP management in mid-adulthood may help slow plaque progression. -
A Large-Scale Genome-wide Association Study of Blood Pressure Accounting for Gene-Depressive Symptomatology Interactions in 564,680 Individuals from Diverse Populations
CONCLUSIONS: Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR. -
From Parents to Children: The Intergenerational Transference of Parents' Sport Club Participation From Childhood to Adolescence: The 40-Year Young Finns Study
CONCLUSIONS: Parents' sports club participation at the age of 9 was favorably associated with their offspring's sports club participation at childhood and early adolescence. Childhood might be one of the most essential periods to conduct physical activity interventions or motivational programs to support children's sports club participation. -
Contribution of autosomal rare and de novo variants to sex differences in autism
Autism is four times more prevalent in males than females. To study whether this reflects a difference in genetic predisposition attributed to autosomal rare variants, we evaluated sex differences in effect size of damaging protein-truncating and missense variants on autism predisposition in 47,061 autistic individuals using a liability model with differing thresholds. Given the sex differences in the rates of cognitive impairment among autistic individuals, we also compared effect sizes of rare... -
Tobacco Smoking in Early Adulthood and Labor Market Performance: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Our findings suggest that smoking had a negative effect on earnings among the younger generation, particularly among the less well-educated. The finding of greater impacts on years of employment among the older age group, particularly among groups with low education levels, is consistent with the delayed onset of most health impacts, which may particularly affect productivity in physically demanding jobs that are more common among people with less education. -
Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology
Mass spectrometry lipidomics is becoming customary to analyze serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known about the consequences of adjusting lipidomics data with lipoprotein measures. We studied 2 population cohorts with 5657 and 2036 participants. Liquid chromatography/tandem mass spectrometry lipidomics was applied to analyze 24 molecular lipid classes and nuclear magnetic resonance spectroscopy to... -
Associations of Cumulative Adulthood, Childhood and Lifelong Insulin With Adulthood Retinal Microvasculature
CONCLUSION: Cumulative childhood, adulthood, and lifelong insulin are associated with decreased retinal arteriolar diameter in adulthood in a population of participants without diabetes, independently of conventional cardiovascular risk factors. -
Early resilience and epigenetic ageing: Results from the prospective Young Finns Study with a 31-year follow-up
Evidence is accumulating on the connection of early adversities and harsh family environment with epigenetic ageing. We investigated whether early psychosocial resilience is associated with epigenetic ageing in adulthood. We used the population-based Young Finns data (n = 1593). Early psychosocial resilience was assessed in 1980-1989 across five broad domains: (1) index of psychological strength (self-esteem at home/in general/at school, perceived possibilities to influence at home, internal... -
Childhood family environment and systemic haemodynamics in adulthood: the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: High childhood socioeconomic family risk predicted adulthood haemodynamic outcomes independently of childhood cardiovascular risk factors and adulthood health behaviours, while other childhood psychosocial adversities were not associated with cardiovascular function in adulthood. -
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic...
2024
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The growing burden of myopia in Europe: evidence from population-based cohorts
Myopia is a childhood-onset condition driven by excessive axial ocular elongation, associated with increased risk of sight-threatening complications and irreversible visual impairment. Despite rising global prevalence, epidemiological data on long-term trends in Europe remain limited. This study examines temporal trends in myopia prevalence and axial length (AL) across European adult birth cohorts. We conducted a comparative birth-cohort analysis using harmonised data from 28 population-based... -
Ultrasound-detected fatty liver in young adults and long-term risk of atherosclerotic cardiovascular disease: The Young Finns Study
CONCLUSIONS: Fatty liver in young adults was associated with incident CHD after adjustment for atherogenic dyslipidaemia and systemic inflammation, with modest attenuation after adjustment for insulin resistance. The association with composite CVD was substantially attenuated after adjustment for apoB. These findings support fatty liver as a marker of later CVD risk in young adults. -
Genetic architecture and cross-platform validation of apolipoprotein A-IV concentrations
CONCLUSION: These results provide a comprehensive overview of the genetic architecture of apoA-IV and suggest mechanistic links to lipid metabolism, kidney function and blood-related traits. Our findings refine the role of apoA-IV as a potential biomarker and inform future epidemiological research. -
Obesity rise plateaus in developed nations and accelerates in developing nations
Global reporting of obesity is commonly based on comparisons over multiple decades¹ and lacks a granular and systematic analysis of its dynamics. We used 4,050 population-based studies with measured height and weight data on 232 million participants to assess the worldwide dynamics of obesity from 1980 to 2024. The rise in obesity decelerated in school-aged children and adolescents throughout the 1990s in many high-income countries, and subsequently plateaued in most at age-standardized... -
Physical Activity Since Childhood and its Association with Changes in Midlife Cognitive Functions: A Longitudinal Prospective Cohort Study
CONCLUSIONS: The results suggest that individuals with higher life-course PA experience a smaller decrease in executive aspects of cognitive function during midlife. -
Personalized Profiling of Lipoprotein and Lipid Metabolism Based on 1018 Measures from Combined Quantitative NMR and LC-MS/MS Platforms
Applications of advanced omics methodologies are increasingly popular in biomedicine. However, large-scale studies aiming at clinical translation are typically siloed to single technologies. Here, we present the first comprehensive large-scale population data combining 209 lipoprotein measures from a quantitative NMR spectroscopy platform and 809 lipid classes and species from a quantitative LC-MS/MS platform. These data with 1018 molecular measures were analyzed in two population cohorts... -
Efficient Search Algorithms for Identifying Synergistic Associations in High-Dimensional Datasets
In recent years, there has been a notably increased interest in the study of multivariate interactions and emergent higher-order dependencies. This is particularly evident in the context of identifying synergistic sets, which are defined as combinations of elements whose joint interactions result in the emergence of information that is not present in any individual subset of those elements. The scalability of frameworks such as partial information decomposition (PID) and those based on... -
Low-Density Lipoprotein Cholesterol Level Distributions Across Different Ages: Implications for Screening Children for Severe and Familial Hypercholesterolemia
No abstract -
Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants
BACKGROUND: Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories. -
Leptin and leptin receptor gene polymorphisms and depression treatment response
CONCLUSION: Our findings suggest that LEPR polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-analyses are needed to confirm the significance of found SNPs and the role of leptin in depression. -
Genetic risk score for coronary artery calcification and its predictive ability for coronary artery disease
CONCLUSIONS: This study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors. -
Early resilience and epigenetic ageing: Results from the prospective Young Finns Study with a 31-year follow-up
Evidence is accumulating on the connection of early adversities and harsh family environment with epigenetic ageing. We investigated whether early psychosocial resilience is associated with epigenetic ageing in adulthood. We used the population-based Young Finns data (n = 1593). Early psychosocial resilience was assessed in 1980-1989 across five broad domains: (1) index of psychological strength (self-esteem at home/in general/at school, perceived possibilities to influence at home, internal... -
Bias in O-Information Estimation
Higher-order relationships are a central concept in the science of complex systems. A popular method of attempting to estimate the higher-order relationships of synergy and redundancy from data is through the O-information. It is an information-theoretic measure composed of Shannon entropy terms that quantifies the balance between redundancy and synergy in a system. However, bias is not yet taken into account in the estimation of the O-information of discrete variables. In this paper, we explain... -
Predicting early-stage coronary artery disease using machine learning and routine clinical biomarkers improved by augmented virtual data
CONCLUSION: Accurate predictions of angiographic CAD can be obtained using a set of routine laboratory markers, age, sex, and smoking status, holding the potential to limit the need for invasive diagnostic techniques. The extension analysis in the YFS demonstrated the potential of these findings in a younger population, and it confirmed applicability to atherosclerotic vascular disease. -
Association of inflammatory cytokines with lung function, chronic lung diseases, and COVID-19
We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular... -
Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns
Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR <... -
General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants
BACKGROUND: Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension. -
Childhood family environment and systemic haemodynamics in adulthood: the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: High childhood socioeconomic family risk predicted adulthood haemodynamic outcomes independently of childhood cardiovascular risk factors and adulthood health behaviours, while other childhood psychosocial adversities were not associated with cardiovascular function in adulthood. -
A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations
Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration... -
Association of Serum Trimethylamine-N-Oxide Concentration from Childhood to Early Adulthood with Age and Sex
CONCLUSIONS: TMAO concentration increased from childhood to early adulthood but was not affected by the given dietary intervention. In females, TMAO concentrations could be directly associated with higher fiber intake suggesting sex-specific differences in TMAO metabolism. -
Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure
CONCLUSION: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP. -
Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations
CONCLUSIONS: Ultra-short-term DFA2 α(1), when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α(1) and SCD is modified by physical exertion. -
Does the effect of adolescent health behaviours on adult cardiometabolic health differ by socioeconomic background? Protocol for a population-based cohort study
INTRODUCTION: Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational... -
HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study
Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol,... -
Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
No abstract -
Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study
CONCLUSIONS: The identified gene module and its members can provide new joint biomarkers for depression and CVH. -
Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data
CONCLUSIONS: By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions. -
Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10^(-8)) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences... -
Genetic causal relationship between immune diseases and migraine: a Mendelian randomization study
CONCLUSION: The evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated. -
Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study
CONCLUSIONS: These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association's ICH score in youth does not. -
NMR metabolomic modeling of age and lifespan: A multicohort analysis
Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear... -
Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
No abstract -
Polymorphisms in <em>ERBB4</em> and <em>TACR1</em> associated with dry mouth in clozapine-treated patients
CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine. -
Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial
CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality... -
The association between GRACE score at admission for myocardial infarction and the incidence of sudden cardiac arrests in long-term follow-up - the MADDEC study
Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December... -
Accumulation of Lewy-Related Pathology Starts in Middle Age: The Tampere Sudden Death Study
When effective treatments against neurodegenerative diseases become a reality, it will be important to know the age these pathologies begin to develop. We investigated alpha-synuclein pathology in brain tissue of the Tampere Sudden Death Study-unselected forensic autopsies on individuals living outside hospital institutions in Finland. Of 562 (16-95 years) participants, 42 were positive for Lewy-related pathology (LRP). The youngest LRP case was aged 54 years, and the frequency of LRP in... -
A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations
Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration... -
Association of childhood socioeconomic status with adulthood maximal exercise blood pressure: the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: These findings suggest that lower childhood family SES is associated with higher maximal exercise BP in adulthood. -
Genome-wide characterization of circulating metabolic biomarkers
Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism^(1-7). This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases^(8-11). Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016... -
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
BACKGROUND: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. -
Gene expression networks regulated by human personality
Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of... -
Effect of weight on depression using multiple genetic instruments
A striking global health development over the past few decades has been the increasing prevalence of overweight and obesity. At the same time, depression has become increasingly common in almost all high-income countries. We investigated whether body weight, measured by body mass index (BMI), has a causal effect on depression symptoms in Finland. Using data drawn from the Cardiovascular Risk in Young Finns Study (N = 1,523, mean age 41.9, SD 5), we used linear regression to establish the... -
Sex differences in coronary atherosclerosis during the pre- and postmenopausal period: The Tampere Sudden Death Study
CONCLUSION: We did not detect any major sex-difference in coronary atherosclerosis in the premenopausal period when women are considered to be protected from CHD. However, in line with CHD mortality statistics, postmenopausal women showed a slower speed of coronary atherosclerosis development compared to men. -
Metabolic syndrome and epigenetic aging: a twin study
CONCLUSIONS: The results of this study suggests that MetS is associated with accelerated epigenetic aging, independent of physical activity, smoking or alcohol consumption, and that the association may be explained by genetics. -
X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized... -
Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern. -
Author Correction: A genomic mutational constraint map using variation in 76,156 human genomes
No abstract -
Polygenic risk for depression predicting temperament trajectories over 15 years - A general population study
CONCLUSIONS: High polygenic risk for major depression may predict differences in temperament trajectories among those who have not developed any severe affective disorders. -
Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits
CONCLUSIONS: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
2023
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Physical Activity Since Childhood and its Association with Changes in Midlife Cognitive Functions: A Longitudinal Prospective Cohort Study
CONCLUSIONS: The results suggest that individuals with higher life-course PA experience a smaller decrease in executive aspects of cognitive function during midlife. -
Factors related to blood-based biomarkers for neurodegenerative diseases and their intergenerational associations in the Young Finns Study: a cohort study
BACKGROUND: Blood-based biomarkers (BBM) of neurodegenerative diseases are emerging as cost-effective tools in the differential diagnostics of Alzheimer's disease and other dementias. Scarce data exist about factors explaining BBM variation in population-based cohorts, and their intergenerational associations are unknown. This study aimed to characterise BBM distributions among a population-based cohort, investigate the association of a wide array of factors with BBM both in midlife and old age,... -
General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participants
BACKGROUND: Adiposity can be measured using BMI (which is based on weight and height) as well as indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions and quantified how well these two metrics discriminate between people with and without hypertension. -
Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial
CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality... -
Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits
CONCLUSIONS: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits. -
Inferring compound heterozygosity from large-scale exome sequencing data
Recessive diseases arise when both copies of a gene are impacted by a damaging genetic variant. When a patient carries two potentially causal variants in a gene, accurate diagnosis requires determining that these variants occur on different copies of the chromosome (that is, are in trans) rather than on the same copy (that is, in cis). However, current approaches for determining phase, beyond parental testing, are limited in clinical settings. Here we developed a strategy for inferring phase for... -
A genomic mutational constraint map using variation in 76,156 human genomes
The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders^(1-4), but attempts to assess constraint for non-protein-coding regions have proved more difficult. Here we aggregate, process and release a dataset of 76,156 human genomes from the Genome Aggregation Database (gnomAD)-the largest public open-access human genome allele frequency reference dataset-and use it to build a genomic... -
Polygenic risk for schizophrenia predicting social trajectories in a general population sample
CONCLUSIONS: Individuals at high PRS(SCZ) (not converted to psychosis) seem to experience a lower preference to be with others over being alone. Individuals with high (v. low) PRS(SCZ) seem to have a similar family structure in terms of partnership status or number of children but, nevertheless, they experience less support from their family. Among those not converted to psychosis in a typical age period, high PRS(SCZ) may predict a 'later risk phase' and reduced functional resilience when... -
Polygenic risk for schizophrenia, social dispositions, and pace of epigenetic aging: Results from the Young Finns Study
Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRS(sch) ) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRS(sch) . The sample came from the population-based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as... -
Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational... -
NMR metabolomic modelling of age and lifespan: a multi-cohort analysis
Metabolomic age models have been proposed for the study of biological aging, however they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. 98 metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈ 31,000 individuals, age range 24-86 years). We used non-linear and... -
Thrombus Aspirates From Patients With Acute Ischemic Stroke Are Infiltrated by Viridans Streptococci
CONCLUSIONS: Oral streptococci were found in aspirated thrombi of patients with acute ischemic stroke as well as in carotid artery samples. Our results suggest that viridans streptococci group bacteria may play a role in the pathophysiology of ischemic stroke. -
Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c
Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that... -
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European... -
A Proposed Pediatric Clinical Cardiovascular Health Reference Standard
CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health. -
Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
No abstract -
Genetic risk scores associated with temperament clusters in Finnish depression patients
CONCLUSION: GRSs seem to associate with an individual's temperament profile, which can be observed in the clusters used. Further research needs to be conducted on these types of clusters and their clinical applicability. -
Genetic insights into resting heart rate and its role in cardiovascular disease
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously... -
Polygenic liabilities underlying job stress and exhaustion over a 10-year follow-up: A general population study
We investigated whether individuals, who have a high polygenic loading for schizophrenia and major depression (PGL) but have not developed the respective disorders, are still susceptible to experience milder forms of ill-being in terms of job strain or exhaustion. We used the population-based Young Finns Study data (n = 928). PGL was assessed with a cumulative score of the polygenic risk scores for schizophrenia and depression. Participants (24-49-year-olds) evaluated their exhaustion levels and... -
Nonalcoholic Fatty Liver Disease Incidence and Remission and Their Predictors During 7 Years of Follow-up Among Finns
CONCLUSION: During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level. -
A causal effects of gut microbiota in the development of migraine
CONCLUSION: Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them. -
High genetic risk for depression as an independent risk factor for mortality in patients referred for coronary angiography
CONCLUSION: A genetic predisposition for depression estimated by a GDRS was independently associated with all-cause and CV mortality in our cohort of patients who had been referred for coronary angiography. No biomarker correlating with the GDRS could be identified. -
Trajectories of cardiovascular risk predict pregnancy outcomes: The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Trajectories of cardiovascular risk, particularly those that represent a consistent or more rapid worsening of cardiovascular health, are associated with a higher risk of pregnancy complications. -
Risk Factors for Ischemic Stroke After Acute Coronary Syndrome
Background Stroke incidence is elevated after acute coronary syndromes (ACS). The aim of this study was to characterize risk factors related to ischemic stroke (IS) after ACS. Methods and Results We conducted a retrospective registry study based on the data of 8049 consecutive patients treated for ACS between 2007 and 2018 in Tays Heart Hospital with a follow-up until December 31, 2020. Potential risk factors were identified by in-depth review of written hospital records and causes-of-death... -
Childhood family environment predicting psychotic disorders over a 37-year follow-up - A general population cohort study
CONCLUSIONS: Our results suggest that childhood family environment and atmosphere patterns as such contribute to the risk for developing adulthood mental disorders with relative disorder specificity. The results emphasize the importance of both individual and public health preventive initiatives, including family support interventions. -
Migraine, chronic kidney disease and kidney function: observational and genetic analyses
Epidemiological studies demonstrate an association between migraine and chronic kidney disease (CKD), while the genetic basis underlying the phenotypic association has not been investigated. We aimed to help avoid unnecessary interventions in individuals with migraine through the investigation of phenotypic and genetic relationships underlying migraine, CKD, and kidney function. We first evaluated phenotypic associations using observational data from UK Biobank (N = 255,896). We then... -
Neighbourhood deprivation in childhood and adulthood and risk of arterial stiffness: the Cardiovascular Risk in Young Finns study
Purpose: Individual socioeconomic status is associated with increased arterial stiffness, but limited data are available on the relations of neighbourhood deprivation with this vascular measure. We prospectively examined whether neighbourhood deprivation in childhood and adulthood predicts arterial stiffness indicated by pulse wave velocity (PWV).Materials and methods: The study population comprised 1,761 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk... -
Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis
CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response. -
Author Correction: The power of genetic diversity in genome-wide association studies of lipids
No abstract -
The relationship of trait-like compassion with epigenetic aging: The population-based prospective Young Finns Study
INTRODUCTION: Helping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity. -
Gene Set Based Integrated Methylome and Transcriptome Analysis Reveals Potential Molecular Mechanisms Linking Cigarette Smoking and Related Diseases
Advanced integrative analysis of DNA methylation and transcriptomics data may provide deeper insights into smoke-induced epigenetic alterations, their effects on gene expression and related biological processes, linking cigarette smoking and related diseases. We hypothesize that accumulation of DNA methylation changes in CpG sites across genomic locations of different genes might have biological significance. We tested the hypothesis by performing gene set based integrative analysis of blood DNA... -
Dissecting the polygenic basis of atherosclerosis via disease-associated cell state signatures
Coronary artery disease (CAD) is a pandemic disease where up to half of the risk is explained by genetic factors. Advanced insights into the genetic basis of CAD require deeper understanding of the contributions of different cell types, molecular pathways, and genes to disease heritability. Here, we investigate the biological diversity of atherosclerosis-associated cell states and interrogate their contribution to the genetic risk of CAD by using single-cell and bulk RNA sequencing (RNA-seq) of... -
A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration
BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. -
Diminishing benefits of urban living for children and adolescents' growth and development
Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being^(1-6). Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5-19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than... -
Stress-Related Exhaustion, Polygenic Cognitive Potential, and Cognitive Test Performance - A General Population Study
CONCLUSION: Stress-related exhaustion, especially if chronic, seems to relate to slower reactions. Co-occurring exhaustion and depression may not have additive effects on cognitive performance. High polygenic cognitive potential may not protect from or predispose to harmful effects of exhaustion or depression on reaction time. -
The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study
CONCLUSION: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes. -
Childhood Dyslipidemia and Carotid Atherosclerotic Plaque in Adulthood: The Cardiovascular Risk in Young Finns Study
Background Childhood exposure to dyslipidemia is associated with adult atherosclerosis, but it is unclear whether the long-term risk associated with dyslipidemia is attenuated on its resolution by adulthood. We aimed to address this question by examining the links between childhood and adult dyslipidemia on carotid atherosclerotic plaques in adulthood. Methods and Results The Cardiovascular Risk in Young Finns Study is a prospective follow-up of children that began in 1980. Since then, follow-up... -
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking... -
OTTERS: a powerful TWAS framework leveraging summary-level reference data
Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to... -
Longitudinal metabolomics of increasing body-mass index and waist-hip ratio reveals two dynamic patterns of obesity pandemic
CONCLUSIONS: Age-associated weight variation in adults between 24 and 49 manifests as temporal divergence in BMI and uniform progression of WHR across metabolic health strata. -
Uncovering the complex genetic architecture of human plasma lipidome using machine learning methods
Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30-45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain... -
Causal relationships between migraine and microstructural white matter: a Mendelian randomization study
CONCLUSIONS: Our findings provided genetic evidence for the causal relationships between migraine and microstructural WM, bringing new insights into brain structure for the development and experience of migraine. -
A new blood based epigenetic age predictor for adolescents and young adults
Children have special rights for protection compared to adults in our society. However, more than 1/4 of children globally have no documentation of their date of birth. Hence, there is a pressing need to develop biological methods for chronological age prediction, robust to differences in genetics, psychosocial events and physical living conditions. At present, DNA methylation is the most promising biological biomarker applied for age assessment. The human genome contains around 28 million DNA... -
Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study
CONCLUSIONS: We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes. -
Cross-sectionally Calculated Metabolic Aging Does Not Relate to Longitudinal Metabolic Changes-Support for Stratified Aging Models
CONCLUSION: The finding is unexpected under the clock hypothesis that would produce a positive correlation between predicted and observed aging. Our results are better explained by a stratified model where aging rates per se are similar in adulthood but differences in starting points explain diverging metabolic fates. -
Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH. -
Genetic analyses implicate complex links between adult testosterone levels and health and disease
CONCLUSIONS: Overall, these findings provide insight into how genetically determined testosterone correlates with several health parameters in both sexes. Yet the lack of evidence for a causal contribution to most traits beyond sex-specific health underscores the complexity of the mechanisms linking testosterone levels to disease risk and sex differences. -
Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study
CONCLUSIONS: These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications. -
Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor...
2022
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Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants
BACKGROUND: Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories. -
Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations
CONCLUSIONS: Ultra-short-term DFA2 α(1), when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α(1) and SCD is modified by physical exertion. -
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
BACKGROUND: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. -
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European... -
A Proposed Pediatric Clinical Cardiovascular Health Reference Standard
CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health. -
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. -
Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis
Only 3-5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with... -
Inflammatory Diseases, Inflammatory Biomarkers, and Alzheimer Disease: An Observational Analysis and Mendelian Randomization
BACKGROUND AND OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of Alzheimer disease (AD) is controversial. We characterized the relationship between inflammatory diseases and risk of AD and explored the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. -
The associations of childhood psychosocial factors with cognitive function in midlife-The young finns study
CONCLUSIONS: The findings suggest an association of childhood psychosocial factors with midlife learning ability and memory. If these links are causal, the results highlight the importance of a child's self-regulation and social adjustment as plausible determinants for adulthood cognitive health. (PsycInfo Database Record (c) 2023 APA, all rights reserved). -
Gene set analysis of transcriptomics data identifies new biological processes associated with early markers of atherosclerosis but not with those of osteoporosis: Atherosclerosis-osteoporosis co/multimorbidity study in the Young Finns Study
CONCLUSIONS: This study identified novel biological processes associated with high CIMT but not with reduced BMD. -
A saturated map of common genetic variants associated with human height
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered... -
Methylation status of <em>VTRNA2-1</em>/<em>nc886</em> is stable across populations, monozygotic twin pairs and in majority of tissues
Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present... -
Temporal variability of serum miR-191, miR-223, miR-128, and miR-24 in multiple sclerosis: A 4-year follow-up study
CONCLUSION: Temporal variability of miR-191-5p and miR-223-3p are associated with changes in disability accumulation and disease activity. While, miR-128-3p was stably expressed and associated with the PPMS subtype and correlated with disability accumulation. -
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for... -
Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we... -
Does social intolerance vary according to cognitive styles, genetic cognitive capacity, or education?
BACKGROUND: Low education, low cognitive abilities, and certain cognitive styles are suggested to predispose to social intolerance and prejudices. Evidence is, however, restricted by comparatively small samples, neglect of confounding variables and genetic factors, and a narrow focus on a single sort of prejudice. We investigated the relationships of education, polygenic cognitive potential, cognitive performance, and cognitive styles with social intolerance in adulthood over a 15-year... -
A genome-wide association study of total child psychiatric problems scores
Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric... -
Rare coding variation provides insight into the genetic architecture and phenotypic context of autism
Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and... -
Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis
Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland's population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for... -
Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: These data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland. -
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow... -
Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including... -
The S1S2S3 electrocardiographic pattern - Prevalence and relation to cardiovascular and pulmonary diseases in the general population
CONCLUSION: In the general adult population, the prevalence of the S1S2S3 ECG pattern is markedly affected by the diagnostic ECG criteria. The S1S2S3-I pattern was associated with hypertension, while S1S2S3-II was associated with heart failure, and both associations were enhanced in men. The associations with other studied cardiovascular and pulmonary diseases were minor and not clinically useful for risk stratification. -
Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis
Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the... -
Elucidating the relationship between migraine risk and brain structure using genetic data
Migraine is a highly common and debilitating disorder that often affects individuals in their most productive years of life. Previous studies have identified both genetic variants and brain morphometry differences associated with migraine risk. However, the relationship between migraine and brain morphometry has not been examined on a genetic level, and the causal nature of the association between brain structure and migraine risk has not been determined. Using the largest available genome-wide... -
Validity of fatty liver disease indices in the presence of alcohol consumption
CONCLUSIONS: Indices perform well and comparably for detection of FLD with alcohol consumption <50 g/day and with different binge-drinking behaviour. -
Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all... -
BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index
CONCLUSION: We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance. -
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with... -
Schizophrenia polygenic risk score and long-term success in the labour market: A cohort study
Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our... -
Evaluation of the QRS score for diagnosing coronary artery disease in women: A Finnish cardiovascular study
CONCLUSIONS: This study suggests that the QRS and ST-segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability. -
Risk Factor Profile in Youth, Genetic Risk, and Adulthood Cognitive Function: The Cardiovascular Risk in Young Finns Study
CONCLUSION: A favourable youth risk factor profile may be beneficial for cognitive function in adulthood, irrespective of genetic propensity for poor cognitive function. -
Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease
CONCLUSIONS: Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD. -
Interatrial block and P terminal force in the general population - Longitudinal changes, risk factors and prognosis
CONCLUSION: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population. -
DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and... -
Magical thinking in individuals with high polygenic risk for schizophrenia but no non-affective psychoses-a general population study
A strong genetic background for psychoses is well-established. Most individuals with a high genetic risk for schizophrenia, however, do not develop the disorder. We investigated whether individuals, who have a high genetic risk for schizophrenia but no non-affective psychotic disorders, are predisposed to develop milder forms of deviant thinking in terms of magical thinking. Participants came from the population-based Young Finns Study (n = 1292). The polygenic risk score for schizophrenia (PRS)... -
Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol
INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This... -
Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults
CONCLUSION: We report absolute and proportional trends for 236 metabolic measures as new reference material for overall age-associated and specific weight-driven changes in real-world populations. -
Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study
BACKGROUND AND OBJECTIVES: Serum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife. -
Genetics of osteopontin in patients with chronic kidney disease: The German Chronic Kidney Disease study
Osteopontin (OPN), encoded by SPP1, is a phosphorylated glycoprotein predominantly synthesized in kidney tissue. Increased OPN mRNA and protein expression correlates with proteinuria, reduced creatinine clearance, and kidney fibrosis in animal models of kidney disease. But its genetic underpinnings are incompletely understood. We therefore conducted a genome-wide association study (GWAS) of OPN in a European chronic kidney disease (CKD) population. Using data from participants of the German... -
Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events
CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.). -
Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
CONCLUSION: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success. -
Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other... -
Does better education mitigate risky health behavior? A mendelian randomization study
Education and risky health behaviors are strongly negatively correlated. Education may affect health behaviors by enabling healthier choices through higher disposable income, increasing information about the harmful effects of risky health behaviors, or altering time preferences. Alternatively, the observed negative correlation may stem from reverse causality or unobserved confounders. Based on the data from the Cardiovascular Risk in Young Finns Study linked to register-based information on... -
Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways
Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium... -
Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment
CONCLUSION: HDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations. -
Multi-Omics Integration in a Twin Cohort and Predictive Modeling of Blood Pressure Values
Abnormal blood pressure is strongly associated with risk of high-prevalence diseases, making the study of blood pressure a major public health challenge. Although biological mechanisms underlying hypertension at the single omic level have been discovered, multi-omics integrative analyses using continuous variations in blood pressure values remain limited. We used a multi-omics regression-based method, called sparse multi-block partial least square, for integrative, explanatory, and predictive... -
Prevalence and long-term prognostic implications of prolonged QRS duration in left ventricular hypertrophy: a population-based observational cohort study
CONCLUSIONS: In ECG-LVH, the risk of excess mortality and new-onset HF markedly increases with longer QRS duration, but even QRS duration within normal limits in ECG-LVH carried a risk of HF compared with the risk in individuals without ECG-LVH. -
Author Correction: Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis
No abstract
2021
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Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10^(-8)) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences... -
The association between GRACE score at admission for myocardial infarction and the incidence of sudden cardiac arrests in long-term follow-up - the MADDEC study
Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December... -
Genetic insights into resting heart rate and its role in cardiovascular disease
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously... -
Assessment of plasma ceramides as predictor for subclinical atherosclerosis
CONCLUSIONS: The new systemic biomarkers, high-risk plasma ceramides and CERT score, showed promising predictive performance for high CIMT with only age and sex as additional variables. This may help in predicting subclinical atherosclerosis for primary prevention. -
Reproductive history and blood cell DNA methylation later in life: the Young Finns Study
CONCLUSIONS: Differences in epigenetic methylation profiles could represent pre-existing risk factors, or changes that occurred as a result of experiencing these complications. -
Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate... -
Meta-analyses identify DNA methylation associated with kidney function and damage
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation... -
The power of genetic diversity in genome-wide association studies of lipids
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use¹. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels², heart disease remains the leading cause of death worldwide³. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets,... -
Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease
CONCLUSIONS: Afamin concentrations are increased in patients with NAFLD and independently predict the development of NAFLD in a population-based cohort. -
Birth weight, adult weight, and cardiovascular biomarkers: Evidence from the Cardiovascular Young Finns Study
This study quantifies the causal effect of birth weight on cardiovascular biomarkers in adulthood using the Cardiovascular Risk in Young Finns Study (YFS). We apply a multivariable Mendelian randomization (MVMR) method that provides a novel approach to improve inference in causal analysis based on a mediation framework. The results show that birth weight is linked to triglyceride levels (β = -0.294; 95% CI [-0.591, 0.003]) but not to low-density lipoprotein (LDL) cholesterol levels (β = 0.007;... -
Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits
Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to... -
Compassion protects against vital exhaustion and negative emotionality
We investigated (i) the predictive relationships of compassion with negative emotionality (a marker of susceptibility to stress) and vital exhaustion (a marker of chronic stress response) and (ii) the effect of compassion on the developmental courses of negative emotionality and vital exhaustion over a follow-up from early adulthood to middle age. We used the prospective Young Finns data (n = 1031-1495, aged 20-50). Compassion was evaluated in 1997, 2001, and 2012; and vital exhaustion and... -
IDO activity forecasts obesity in males and premenopausal females in a 10-year follow-up study:The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: IDO activity correlated with obesity and factors related to NAFLD, namely obesity of visceral type, hypertriglyceridemia and CRP (in females), well-characterized risk factors for diabetes and atherosclerosis in 6- and 10-year follow-up in males and premenopausal females. -
Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood: the cardiovascular risk in young Finns study
CONCLUSION: Childhood BMI, blood glucose, vegetable consumption, smoking and physical activity independently predict systemic vascular resistance in adulthood. A favourable change in the number of risk factors or BMI from childhood to adulthood was associated with lower vascular resistance in adulthood. -
C-reactive protein and temperament: An instrumental variable analysis
CONCLUSIONS: We found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits. -
Association between Oral Pathology, Carotid Stenosis, and Oral Bacterial DNA in Cerebral Thrombi of Patients with Stroke
CONCLUSIONS: Stroke patients had poor oral health which tended to associate with their carotid artery stenosis. Although oral streptococcal DNA was found in thrombus aspirates and carotid endarterectomy samples, the amount of oral streptococcal DNA in thrombus aspirates was the lowest among those with the most severe oral pathology. These results suggest that the association between poor oral health and acute ischemic stroke is linked to carotid artery atherosclerosis. -
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested)... -
Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants
BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. -
Genetic differential susceptibility to the parent-child relationship quality and the life span development of compassion
The development of compassion for others might be influenced by the social experiences made during childhood and has a genetic component. No research has yet investigated whether the parent-child relationship quality interacts with genetic variation in the oxytocin and dopamine systems in predicting compassion over the life span. In the prospective Young Finns Study (N = 2099, 43.9% men), we examined the interaction between mother-reported emotional warmth and intolerance toward their child... -
RSPO3 is important for trabecular bone and fracture risk in mice and humans
With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm... -
Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course
We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12-70 years, Australia: 16-73 years), with observations at the focus... -
Addendum: The mutational constraint spectrum quantified from variation in 141,456 humans
No abstract -
Genetic association study of childhood aggression across raters, instruments, and age
Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and... -
Publisher Correction: Identification of 371 genetic variants for age at first sex and birth linked to externalising behavior
No abstract -
Human Prostate Tissue MicroRNAs and Their Predicted Target Pathways Linked to Prostate Cancer Risk Factors
MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate... -
Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs
CONCLUSIONS: These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region. -
Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations
CONCLUSIONS: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479. -
Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia
Activation of the hypoxia-inducible factor (HIF) pathway reprograms energy metabolism. Hemoglobin (Hb) is the main carrier of oxygen. Using its normal variation as a surrogate measure for hypoxia, we explored whether lower Hb levels could lead to healthier metabolic profiles in mice and humans (n = 7175) and used Mendelian randomization (MR) to evaluate potential causality (n = 173,480). The results showed evidence for lower Hb levels being associated with lower body mass index, better glucose... -
Birth weight and adult income: An examination of mediation through adult height and body mass
This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically... -
The Timing and Sequence of Cardiovascular Health Decline
CONCLUSIONS: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. -
Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the... -
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity. -
Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study
CONCLUSIONS: The newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results. -
Variants associated with <em>HHIP</em> expression have sex-differential effects on lung function
Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought... -
Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study
CONCLUSION: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases. -
Meta-analysis of epigenome-wide association studies of carotid intima-media thickness
Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG... -
Influential Periods in Longitudinal Clinical Cardiovascular Health Scores
The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project)... -
Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood. -
Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health
Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for... -
Functional Polymorphisms in Oxytocin and Dopamine Pathway Genes and the Development of Dispositional Compassion Over Time: The Young Finns Study
Background: We define compassion as an enduring disposition that centers upon empathetic concern for another person's suffering and the motivation to act to alleviate it. The contribution of specific candidate genes to the development of dispositional compassion for others is currently unknown. We examine candidate genes in the oxytocin and dopamine signaling pathways. Methods: In a 32-year follow-up of the Young Finns Study (N = 2,130, 44.0% men), we examined with multiple indicators latent... -
Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes
No abstract -
Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df)... -
Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia
CONCLUSIONS AND RELEVANCE: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM. -
Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis
CONCLUSIONS: Our findings suggest that childhood adiposity predominantly exerts its detrimental effect on adult systemic metabolism along a pathway that involves adulthood body size. -
Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study
We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the... -
The relationship of socioeconomic status in childhood and adulthood with compassion: A study with a prospective 32-year follow-up
The objective of this study was to investigate (i) whether childhood family SES predicts offspring's compassion between ages 20-50 years and (ii) whether adulthood SES predicts compassion or vice versa. We used the prospective population-based Young Finns data (N = 637-2300). Childhood family SES was evaluated in 1980; participants' adulthood SES in 2001 and 2011; and compassion for others in 1997, 2001, and 2012. Compassion for others was evaluated with the Compassion scale of the Temperament... -
Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total... -
Cardiovascular Risk Factors in Childhood and Left Ventricular Diastolic Function in Adulthood
CONCLUSIONS: Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood. -
Associations of Serum Fatty Acid Proportions with Obesity, Insulin Resistance, Blood Pressure, and Fatty Liver: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: High serum percentages of total SFAs and MUFAs and low PUFAs, but also several specific FAs, predict future unfavorable cardiometabolic outcomes in Finnish adults.
2020
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Adolescent weight gain trajectories and their associations with biological aging: a genetically informed study
CONCLUSIONS: Our findings indicate that high BMI in adolescence may accelerate biological aging, especially in individuals with a genetic predisposition to high BMI. Adolescents with a genetic susceptibility to high BMI and elevated BMI might be prone to obesity-related health risks, highlighting early prevention strategies' importance. -
Early life and adulthood risk factors for middle age P-wave prolongation and left atrial enlargement
CONCLUSION: Excess BMI from childhood through adulthood is a key determinant of atrial remodelling in middle age. These findings highlight the long-term impact of early life adiposity and underscore the importance of lifelong weight management in preventing atrial cardiomyopathy and its clinical sequelae. -
Traditional Disease Risk Factors Outperform Epigenetic Clocks as Predictors of Non-Communicable Disease Morbidity in a Middle-Aged Cohort
DNA methylation-based epigenetic clocks have been highlighted as promising biomarkers of ageing, and they have been shown to robustly predict morbidity and mortality. However, current literature is lacking a formal analysis of the increased prediction accuracy, or the added value, of the epigenetic clocks over traditional risk factors, such as body composition, smoking, or alcohol consumption, in predicting common chronic diseases. Here, we have compared the most commonly used epigenetic clocks... -
Prognostic potential of circulatory miR-19a-3p, miR-19b-3p, and miR-329-3p for future hypertension diagnosis
MicroRNAs have been suggested as essential hypertension biomarkers, but evidence remains inconclusive due to limited high-throughput studies in population cohorts. We analyzed data from the Young Finns Study (YFS) from 2011 and 2018-2020 to assess cross-sectional and prospective associations between circulatory microRNAs, blood pressure (BP), and hypertension. Hypertension risk prediction potential was assessed using nested logistic and Weibull survival models; model performance was evaluated... -
Meta-analysis of genome-wide association studies of food allergy and IgE sensitization
CONCLUSION: This study identified 37 single nucleotide polymorphisms suggestively associated with FA and demonstrated genetic differences across phenotypes. It highlights the need for a unified FA definition and sheds light on FA's shared genetic architecture with allergies. -
Neighbourhood socioeconomic disadvantage from childhood to midlife and carotid atherosclerosis
CONCLUSIONS: Long-term exposure to neighbourhood socioeconomic disadvantage beginning in childhood is associated with subclinical atherosclerosis in midlife, independently of achieved socioeconomic position. These findings highlight the importance of cumulative socioeconomic environments across the life course and suggest that behavioural risk factors may partly explain observed neighbourhood-level associations with atherosclerosis. -
Cohort Profile Update: Expanding the Cardiovascular Risk in Young Finns Study into a multigenerational cohort
No abstract -
Genome-wide DNA methylation patterns for indicators of liver steatosis: a longitudinal multiomic study
CONCLUSIONS: Our findings highlight the association between the methylation levels of cg06690548 (SLC7A11) and liver steatosis, describe the dynamic relationship between whole blood DNA methylation and MASLD, and contribute to a deeper understanding of the pathophysiology of liver diseases. -
Life-Course Blood Pressure Levels, 38-Year Tracking, and Prediction of Hypertension
CONCLUSIONS: These data indicate that long-term cumulative exposure to elevated BP levels in childhood/adolescence are associated with a substantially increased risk of adult hypertension. -
Differential effects of adolescent health behaviours on adult cardiometabolic health by parental and neighbourhood socioeconomic background
Adolescent healthy behaviours may improve cardiometabolic health in adulthood differently across socioeconomic groups. We aimed to quantify the effects of adolescent healthy behaviours on multiple biomarkers of adult cardiometabolic health by socioeconomic backgrounds. We used a population-based cohort of Finnish adolescents from the Young Finns Study (1980-89, n = 2984) followed into adulthood (2001-11). Healthy behaviours (no smoking, no alcohol consumption, sufficient physical activity, daily... -
A multilayer network analysis of cardiovascular-depression comorbidity reveals symptom-specific molecular biomarkers
CONCLUSIONS: This network-based analysis revealed symptom-specific biological pathways linking CVD and depression. The identified biomarkers may offer insights into shared mechanisms and support future prevention and treatment strategies for cardiometabolic-psychiatric comorbidity. -
Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus
Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed trans expression quantitative trait locus (trans-eQTL) meta-analysis in 3734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset of 682 individuals. The trans-eQTL signal at the ubiquitin specific... -
Electrocardiogram markers predicting ischemic stroke after acute coronary syndrome
CONCLUSIONS: ECG markers demonstrating LV dysfunction, LVH and atriopathy associate with IS risk after ACS, although external validation is still required. -
Polygenic prediction of body mass index and obesity through the life course and across ancestries
Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European... -
Life-course neighbourhood socioeconomic disadvantage and atherosclerotic carotid artery plaques. The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Long-term exposure to neighbourhood socioeconomic disadvantage beginning in childhood is associated with subclinical atherosclerosis in midlife independently of achieved socioeconomic position. Behavioural risk factors partially mediate this link, highlighting the importance of early and sustained interventions targeting both social environments and health behaviours to mitigate cardiovascular risk. -
Factors related to blood-based biomarkers for neurodegenerative diseases and their intergenerational associations in the Young Finns Study: a cohort study
BACKGROUND: Blood-based biomarkers (BBM) of neurodegenerative diseases are emerging as cost-effective tools in the differential diagnostics of Alzheimer's disease and other dementias. Scarce data exist about factors explaining BBM variation in population-based cohorts, and their intergenerational associations are unknown. This study aimed to characterise BBM distributions among a population-based cohort, investigate the association of a wide array of factors with BBM both in midlife and old age,... -
Tracking and Trajectory Analysis of Active Commuting from Childhood to Midlife
CONCLUSIONS: Tracking of AC from childhood to mid-adulthood was low to moderately high. Stable and increasing AC trajectories predicted higher adult PA levels during weekdays or weekends. -
Childhood 25-hydroxy-vitamin D levels predict early cardiovascular outcomes in adulthood: the Cardiovascular Risk in Young Finns Study
No abstract -
Blood pressure in childhood, young- and mid-adulthood: association with carotid plaque severity
CONCLUSIONS: Blood pressure at each life stage contributes equally to carotid plaque presence, with mid-adulthood BP associated with a greater contribution to plaque area. These findings underscore the importance of maintaining normal BP throughout life to reduce atherosclerosis risk and suggest that intensive BP management in mid-adulthood may help slow plaque progression. -
Association of neighborhood and individual-level socioeconomic disadvantage in childhood and adulthood with cognitive function in mid-adulthood: Cardiovascular Risk in Young Finns Study
Socioeconomic disadvantage at individual level is associated with poor cognitive outcomes but the link of neighborhood disadvantage with cognitive function is unclear. We used data from Young Finns Study, a population-based cohort, to examine the associations of neighborhood and individual-level disadvantage in childhood (age 3-21 years) and adulthood (age 22 up to the time of cognitive assessment) with cognitive function in mid-adulthood (age 35-49 years). Neighborhood disadvantage was... -
From Parents to Children: The Intergenerational Transference of Parents' Sport Club Participation From Childhood to Adolescence: The 40-Year Young Finns Study
CONCLUSIONS: Parents' sports club participation at the age of 9 was favorably associated with their offspring's sports club participation at childhood and early adolescence. Childhood might be one of the most essential periods to conduct physical activity interventions or motivational programs to support children's sports club participation. -
Tobacco Smoking in Early Adulthood and Labor Market Performance: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Our findings suggest that smoking had a negative effect on earnings among the younger generation, particularly among the less well-educated. The finding of greater impacts on years of employment among the older age group, particularly among groups with low education levels, is consistent with the delayed onset of most health impacts, which may particularly affect productivity in physically demanding jobs that are more common among people with less education. -
Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology
Mass spectrometry lipidomics is becoming customary to analyze serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known about the consequences of adjusting lipidomics data with lipoprotein measures. We studied 2 population cohorts with 5657 and 2036 participants. Liquid chromatography/tandem mass spectrometry lipidomics was applied to analyze 24 molecular lipid classes and nuclear magnetic resonance spectroscopy to... -
Associations of Cumulative Adulthood, Childhood and Lifelong Insulin With Adulthood Retinal Microvasculature
CONCLUSION: Cumulative childhood, adulthood, and lifelong insulin are associated with decreased retinal arteriolar diameter in adulthood in a population of participants without diabetes, independently of conventional cardiovascular risk factors. -
Efficient Search Algorithms for Identifying Synergistic Associations in High-Dimensional Datasets
In recent years, there has been a notably increased interest in the study of multivariate interactions and emergent higher-order dependencies. This is particularly evident in the context of identifying synergistic sets, which are defined as combinations of elements whose joint interactions result in the emergence of information that is not present in any individual subset of those elements. The scalability of frameworks such as partial information decomposition (PID) and those based on... -
Early resilience and epigenetic ageing: Results from the prospective Young Finns Study with a 31-year follow-up
Evidence is accumulating on the connection of early adversities and harsh family environment with epigenetic ageing. We investigated whether early psychosocial resilience is associated with epigenetic ageing in adulthood. We used the population-based Young Finns data (n = 1593). Early psychosocial resilience was assessed in 1980-1989 across five broad domains: (1) index of psychological strength (self-esteem at home/in general/at school, perceived possibilities to influence at home, internal... -
Bias in O-Information Estimation
Higher-order relationships are a central concept in the science of complex systems. A popular method of attempting to estimate the higher-order relationships of synergy and redundancy from data is through the O-information. It is an information-theoretic measure composed of Shannon entropy terms that quantifies the balance between redundancy and synergy in a system. However, bias is not yet taken into account in the estimation of the O-information of discrete variables. In this paper, we explain... -
Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations
CONCLUSIONS: Ultra-short-term DFA2 α(1), when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α(1) and SCD is modified by physical exertion. -
NMR metabolomic modeling of age and lifespan: A multicohort analysis
Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear... -
Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study
CONCLUSIONS: These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association's ICH score in youth does not. -
Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial
CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality... -
Sex differences in coronary atherosclerosis during the pre- and postmenopausal period: The Tampere Sudden Death Study
CONCLUSION: We did not detect any major sex-difference in coronary atherosclerosis in the premenopausal period when women are considered to be protected from CHD. However, in line with CHD mortality statistics, postmenopausal women showed a slower speed of coronary atherosclerosis development compared to men. -
A Proposed Pediatric Clinical Cardiovascular Health Reference Standard
CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health. -
Risk Factors for Ischemic Stroke After Acute Coronary Syndrome
Background Stroke incidence is elevated after acute coronary syndromes (ACS). The aim of this study was to characterize risk factors related to ischemic stroke (IS) after ACS. Methods and Results We conducted a retrospective registry study based on the data of 8049 consecutive patients treated for ACS between 2007 and 2018 in Tays Heart Hospital with a follow-up until December 31, 2020. Potential risk factors were identified by in-depth review of written hospital records and causes-of-death... -
Diminishing benefits of urban living for children and adolescents' growth and development
Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being^(1-6). Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5-19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than... -
Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study
CONCLUSIONS: These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications. -
Parenthood and changes in physical activity from early adulthood to mid-life among Finnish adults
This study examined longitudinal associations between parenthood-related factors and physical activity from young adulthood to midlife over a 19-year follow-up period. Participants (n = 761) at the ongoing Cardiovascular Risk in Young Finns Study responded to a self-report questionnaire in their adulthood (in 1992, 2001, 2007, and 2011). Participants were classified as meeting or not meeting an aerobic physical activity recommendation. Parenthood-related factors included the age of having their... -
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. -
The associations of childhood psychosocial factors with cognitive function in midlife-The young finns study
CONCLUSIONS: The findings suggest an association of childhood psychosocial factors with midlife learning ability and memory. If these links are causal, the results highlight the importance of a child's self-regulation and social adjustment as plausible determinants for adulthood cognitive health. (PsycInfo Database Record (c) 2023 APA, all rights reserved). -
A saturated map of common genetic variants associated with human height
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered... -
Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with... -
Evaluation of the QRS score for diagnosing coronary artery disease in women: A Finnish cardiovascular study
CONCLUSIONS: This study suggests that the QRS and ST-segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability. -
Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol
INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This... -
Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits
Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to... -
Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs
CONCLUSIONS: These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region. -
The Timing and Sequence of Cardiovascular Health Decline
CONCLUSIONS: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. -
Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study
CONCLUSIONS: The newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results. -
Variants associated with <em>HHIP</em> expression have sex-differential effects on lung function
Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought... -
Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia
CONCLUSIONS AND RELEVANCE: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.
2019
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Polygenic prediction of body mass index and obesity through the life course and across ancestries
Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European... -
Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids
Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of... -
Tobacco Smoking in Early Adulthood and Labor Market Performance: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Our findings suggest that smoking had a negative effect on earnings among the younger generation, particularly among the less well-educated. The finding of greater impacts on years of employment among the older age group, particularly among groups with low education levels, is consistent with the delayed onset of most health impacts, which may particularly affect productivity in physically demanding jobs that are more common among people with less education. -
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk. -
A saturated map of common genetic variants associated with human height
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered... -
Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants
BACKGROUND: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. -
The Timing and Sequence of Cardiovascular Health Decline
CONCLUSIONS: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. -
Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the... -
Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia
CONCLUSIONS AND RELEVANCE: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM. -
Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D. -
Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants
BACKGROUND: Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. -
Comparison of 2 fully automated tests detecting antibodies against nucleocapsid N and spike S1/S2 proteins in COVID-19
Automated assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in coronavirus disease 2019 (COVID-19) diagnostics have recently come available. We compared the performance of the Elecsys® Anti-SARS-CoV-2 and LIAISON® SARS-CoV-2 S1/S2 IgG tests. The seroconversion panel comprised of 120 samples from 13 hospitalized COVID-19 patients. For the sensitivity and specificity testing, samples from COVID-19 outpatients >15 days after positive nucleic acid... -
Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes
Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome... -
The mutational constraint spectrum quantified from variation in 141,456 humans
Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant... -
Cardiovascular Health Trajectories From Childhood Through Middle Age and Their Association With Subclinical Atherosclerosis
CONCLUSIONS AND RELEVANCE: In this study, CVH declined from childhood into adulthood. Promoting and preserving ideal CVH from early life onward may be associated with reduced CVD risk later in life. -
Long-term prognostic significance of the ST level and ST slope in the 12‑lead ECG in the general population
CONCLUSION: Lower ST level in the lateral ECG leads is an independent prognostic factor to predict all-cause mortality in the general population. -
Influence of Genetic Variation in <em>PDE3A</em> on Endothelial Function and Stroke
We aimed to characterize the genetics of endothelial function and how this influences risk for cardiovascular diseases such as ischemic stroke. We integrated genetic data from a study of ultrasound flow-mediated dilatation of brachial artery in adolescents from ALSPAC (Avon Longitudinal Study of Parents and Children; n=5214) with a study of ischemic stroke (MEGASTROKE: n=60 341 cases and 452 969 controls) to identify variants that confer risk of ischemic stroke through altered endothelial... -
Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition
Cholesteryl ester transfer protein (CETP) inhibition reduces vascular event risk, but confusion surrounds its effects on low-density lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic inhibition of CETP on detailed lipoprotein measures and compare those to genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We used an allele associated with lower CETP expression (rs247617) to mimic CETP inhibition and an allele associated with lower HMGCR... -
Childhood risk factors and carotid atherosclerotic plaque in adulthood: The Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis. -
RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease
Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with... -
The association between charlson comorbidity index and mortality in acute coronary syndrome - the MADDEC study
Objectives. Acute coronary syndrome (ACS) is associated with high mortality. Charlson comorbidity index (CCI) was designed over 30 years ago to measure the impact of pre-existing comorbidities on long-term survival of the patient. We wanted to re-evaluate the performance of CCI and its components in modern setting. Design. This is a retrospective study of 1576 consecutive patients undergoing invasive evaluation and treated for ACS in single tertiary center between 2015-2016. Mortality was... -
Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis: The Cardiovascular Risk in Young Finns Study
CONCLUSION: This study identified a novel lipid module associated with both surrogate markers of both subclinical osteoporosis and subclinical atherosclerosis. Alterations in the metabolism of the identified lipid module and, more specifically, the TAG related molecular lipids within the module may provide potential new biomarkers for testing the comorbidities, opening avenues for the emergence of dual-purpose prevention measures. -
Three genetic-environmental networks for human personality
Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized... -
Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration
Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint... -
Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy
Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed... -
Combination of low blood pressure response, low exercise capacity and slow heart rate recovery during an exercise test significantly increases mortality risk
Aims: We investigated the combination of low systolic blood pressure (SBP) response, low exercise capacity (EC) and slow heart rate recovery (HRR) during an exercise test in mortality prediction.Patients and methods: Our population consisted of 3456 patients from the Finnish Cardiovascular Study. A failure of SBP to increase >42 mmHg was defined as a low response. Low EC was defined as < 8 metabolic equivalents. 1-minute HRR ≤18 bpm from maximum was defined as slow HRR.Results: During a median... -
Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts
CONCLUSIONS/INTERPRETATION: Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk. -
Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for... -
Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study
CONCLUSIONS AND RELEVANCE: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms. -
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an... -
Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis
CONCLUSIONS: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity. -
A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity
Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old)... -
Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology
No abstract -
Exposure to heavy physical work from early to later adulthood and primary healthcare visits due to musculoskeletal diseases in midlife: a register linked study
CONCLUSIONS: To reduce burden of musculoskeletal diseases, preventive actions to reduce exposure to or mitigate the consequences of physically heavy work throughout the work career are needed. -
CVD risk factors and surrogate markers - Urban-rural differences
Aims: Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban-rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). Methods: The study population comprised 2903 participants (54.1% female, mean age 10.5... -
Gene expression profiles of TNF-like cytokine 1A (TL1A) and its receptors death receptor 3 (DR3) and decoy receptor 3 (DcR3) in multiple sclerosis
TL1A/DR3/DcR3 pathway is an important mediator of inflammatory responses and contributes to the pathogenesis of several chronic inflammatory diseases. Therefore, we analysed PBMC gene expression of these molecules in 30 relapsing-remitting multiple sclerosis (RRMS) patients, 8 secondary progressive MS (SPMS), 9 primary progressive MS (PPMS), 11 clinically isolated syndrome (CIS) patients, and 16 healthy controls (HCs), to evaluate their biomarker potential in MS. The results showed significant... -
Age-dependent association of gut bacteria with coronary atherosclerosis: Tampere Sudden Death Study
CONCLUSIONS: DNA of the Clostridium leptum group and pathogenic Enterobactericeae increase in the gut microbiome with age and can be detected in the same individual's coronary plaques along with pathogenic Streptococcus spp., associating with more severe coronary atherosclerosis. -
Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta-Analysis of 19 005 Individuals
CONCLUSION: Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants. -
Cardiorespiratory fitness and heart rate recovery predict sudden cardiac death independent of ejection fraction
CONCLUSIONS: CRF and HRR are significantly associated with the risk of SCD regardless of LVEF. -
A meta-analysis of genome-wide association studies identifies multiple longevity genes
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358... -
New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders
Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d^(-1)) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We... -
Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits
Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures,... -
Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents
CONCLUSIONS: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty. -
Long-term and recent trends in hypertension awareness, treatment, and control in 12 high-income countries: an analysis of 123 nationally representative surveys
BACKGROUND: Antihypertensive medicines are effective in reducing adverse cardiovascular events. Our aim was to compare hypertension awareness, treatment, and control, and how they have changed over time, in high-income countries. -
Left ventricular ejection fraction adds value over the GRACE score in prediction of 6-month mortality after ACS: the MADDEC study
CONCLUSIONS: Adding LVEF to the GRACE score significantly improves risk prediction of 6-month mortality after ACS. -
New evidence from plasma ceramides links apoE polymorphism to greater risk of coronary artery disease in Finnish adults
apoE, a key regulator of plasma lipids, mediates altered functionalities in lipoprotein metabolism and thus affects the risk of coronary artery disease (CAD). The significance of different apoE polymorphisms remains unclear; although the ε4 allele is clearly associated with increased cholesterol levels (which inform CAD risk), direct studies about apoE polymorphisms on CAD risk and development have yielded controversial results. Furthermore, certain species of ceramides-complex lipids abundant... -
Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals
CONCLUSIONS: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation... -
Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes
We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status... -
Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns
CONCLUSION: The present results extend the knowledge about genetic factors contributing to the inflammatory load. Our findings suggest that two distinct mechanisms contribute to the soluble adhesion molecule levels in the ABO locus and that elevated soluble adhesion molecule levels per se may not increase risk for cardiovascular disease.