Julkaisut
2026
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Associations of Accumulating Physical Activity and Sedentary Time From Childhood to Adolescence With Arterial Stiffness and Structure in Adolescence-An 8-Year Follow-Up Study
CONCLUSION: In girls, higher PA, especially moderate to vigorous PA, may slow arterial stiffening, whereas boys may already be physically active beyond levels that yield further benefits. -
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... -
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. -
Multi-National Evaluation of Low-Density Lipoprotein Cholesterol Equations in Young Adulthood for Long-Term Risk of Atherosclerotic Cardiovascular Disease
CONCLUSIONS: The Martin-Hopkins equation provides more accurate LDL-C-based risk classification, identifying high-risk young adults missed by other equations and minimizing misclassification of those at normal risk. -
Population-scale immune multiome atlas reveals regulatory disease mechanisms
Most disease-associated genetic variants lie in non-coding regions^(1,2), yet mechanistic insights are limited by the lack of an empirical framework for characterizing the molecular consequences of regulatory variation. Single-cell molecular quantitative trait locus (QTL) mapping^(3,4) connects variants to gene regulation but lacks the power and simultaneous measurements to trace mechanisms from chromatin to expression⁵. Here we show that population-scale simultaneous profiling of chromatin... -
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. -
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. -
XXYLT1 and Mendelian Retinal Dystrophy
CONCLUSIONS AND RELEVANCE: This GWAS identified an association between XXYLT1 and IRD. These results affirm that GWAS in a founder population can be used as a potential tool for the discovery of rare mendelian disease genes and that XXYLT1 should be considered in clinical IRD gene panels. -
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. -
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. -
Polygenic Risk Impacts Lifetime Risk and Prognosis of Glaucoma
CONCLUSIONS: In this large biobank study, a glaucoma PRS effectively stratified individuals according to their lifetime risk of glaucoma, with substantial stratification evident already by midlife. The PRS provided a more precise risk assessment than family history alone, and it was effective in stratifying individuals based on several prognostic measures, including medical treatment escalation and surgical interventions. These findings support the potential usefulness of PRS-guided screening... -
Association and risk prediction of 19 complex diseases with polygenic scores and socioeconomic status
CONCLUSIONS: Genetic variation and social circumstances are linked to differences in disease risk both independently, and in combination with one another. Considering both factors modestly improves identification of higher-risk groups and highlights the value of accounting for social context alongside inherited variation in population-level assessments.
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. -
Genetic liability to psoriasis predicts severe disease outcomes
CONCLUSIONS: The psoriasis susceptibility PRS demonstrates utility and may be more effective than established epidemiological factors, as a stratification tool to identify those individuals that are at greatest risk of severe disease and may benefit most from early intervention. -
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. -
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... -
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,... -
Associations of Physical Activity and Dietary Fat Quality With Arterial Health in Adolescents
CONCLUSION: MVPA and PAEE were related to better arterial health. Moreover, our results suggest that higher PAEE benefits adolescents with higher SFA intake. -
Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty
Frailty is a clinically relevant phenotype with notable gaps in our understanding of its etiology. Using the Hospital Frailty Risk Score (HFRS) to define frailty, we performed a genome-wide association study in FinnGen (N = 500,737), replicated the results in the UK Biobank (N = 407,463) and performed a meta-analysis. We prioritized genes through colocalization with expression, splicing and protein quantitative trait loci and proteomics integration. We identified 53 independent lead variants... -
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... -
Genetic Loci Associated With Periodontitis: The FinnGen Study Based on National Health Registers
CONCLUSIONS: Our GWAS suggests that genetic variation contributing to immune dysregulation is involved in the pathogenesis of periodontitis, which has considerable genetic similarity with other complex traits. -
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,... -
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.
2024
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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... -
Novel loci and biomedical consequences of iron homoeostasis variation
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression,... -
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... -
Associations of Cardiovascular Health Metrics in Childhood and Adolescence With Arterial Health Indicators in Adolescence: The PANIC Study
CONCLUSIONS: While our results suggest that higher cardiometabolic risk factors in childhood may exert unfavorable effects on arterial health during adolescence, we demonstrated the complexity of relationships between cardiovascular health metrics and arterial health indicators in childhood and adolescence. We found different associations of cardiovascular health metrics with cIMT and PWV in childhood and adolescence, calling for caution when interpreting the results of various cardiovascular... -
Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations
Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identify 41... -
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... -
Predictors in Youth of Adult Cardiovascular Events
CONCLUSIONS: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted adult cardiovascular events. The addition of lipid measurements to nonlaboratory risk factors did not improve the prediction of cardiovascular events. -
Cognitive performance from childhood to old age and intergenerational correlations in the multigenerational Young Finns Study
CONCLUSION: This study describes the natural course of cognitive performance across the lifespan and proves that cognitive performance changes differently across cognitive domains with weak intergenerational transmission. -
Life-period associations of body mass index with adult carotid intima-media thickness: The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study
CONCLUSION: Although our data suggest sensitive periods in the life-course where prevention and intervention aimed at reducing BMI might provide most benefit in limiting the effects of BMI on cIMT, maintaining lower BMI across the life-course appears to be optimal. -
Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis
Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk¹. Furthermore, LDL-C fluctuations are associated with ASCVD outcomes^(2-4). However, the precise mechanisms behind this increased ASCVD risk are not understood. Here we find... -
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 <... -
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. -
Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort
BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).
2023
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Association of number of siblings with preclinical markers of cardiovascular disease. The cardiovascular risk in Young Finns study
To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood. The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3-18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and... -
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... -
NTHL1 is a recessive cancer susceptibility gene
In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome Aggregation Database. Additionally, we carried out a validation study of SERPINA3 c.918-1G>C, recently suggested for BC predisposition. We estimated the frequencies of 41 rare candidate variants in 38 genes by genotyping them in 2482-4101 BC patients and... -
Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events
CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical... -
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... -
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. -
High compassion predicts fewer sleep difficulties: A general population study with an 11-year follow-up
INTRODUCTION: This study investigated the cross-sectional and longitudinal associations between self-reported compassion and sleep quality. -
A FinnGen pilot clinical recall study for Alzheimer's disease
Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer's disease (AD). This study describes a process for clinical recall studies from FinnGen.... -
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. -
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. -
Data Resource Profile: Nationwide registry data for high-throughput epidemiology and machine learning (FinRegistry)
No abstract
2022
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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... -
Exercise-induced bronchoconstriction is associated with air humidity and particulate matter concentration in preschool children
CONCLUSIONS: Even low PM(2.5) levels may have an effect on EIB in children. Of the other properties of air, only AH was associated with the incidence of EIB. -
Long-term residential sunlight exposure associated with cognitive function among adults residing in Finland
While sunlight may influence cognitive function through several pathways, associations of residential sunlight exposure with cognitive function are not well known. We evaluated associations of long-term residential sunlight exposure with cognitive function among a representative cohort of 1838 Finnish adults residing in Finland who underwent comprehensive cognitive assessment in midlife. We linked daily recordings of global solar radiation to study participants using residential information and... -
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... -
Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires: lessons from a pilot study within FinnGen
CONCLUSION: In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting. -
Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study
CONCLUSIONS: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population. -
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... -
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...
2021
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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. -
Outdoor pollen concentration is not associated with exercise-induced bronchoconstriction in children
CONCLUSIONS: In our large clinical sample, outdoor air pollen concentration was not associated with the probability of exercise-induced bronchoconstriction in free running test in children while low absolute humidity was the best predictor of airway obstruction. -
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. -
Long-term cumulative light exposure from the natural environment and sleep: A cohort study
We analysed (A) the association of short-term as well as long-term cumulative exposure to natural light, and (B) the association of detailed temporal patterns of natural light exposure history with three indicators of sleep: sleep duration, sleep problems, and diurnal preference. Data (N = 1,962; 55% women; mean age 41.4 years) were from the prospective Young Finns Study, which we linked to daily meteorological data on each participant's neighbourhood natural light exposure using residential... -
Rewards of Compassion: Dispositional Compassion Predicts Lower Job Strain and Effort-Reward Imbalance Over a 11-Year Follow-Up
Dispositional compassion has been shown to predict higher well-being and to be associated with lower perceived stress and higher social support. Thus, compassion may be a potential individual factor protecting from job strain. The current study examines (i) whether dispositional compassion predicts job strain and effort-reward imbalance (ERI) or does the predictive relationship run from job strain and ERI to dispositional compassion and (ii) the effect of dispositional compassion on the... -
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. -
Prevalence Implications of the 2017 American Academy of Pediatrics Hypertension Guideline and Associations with Adult Hypertension
CONCLUSIONS: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension. -
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. -
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)... -
Within-visit SBP variability from childhood to adulthood and markers of cardiovascular end-organ damage in mid-life
CONCLUSION: Within-visit SBP variability from childhood to adulthood does not provide additional predictive utility over SBP over the same period of the life course. -
Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in <em>MUC5B</em> mutation carriers
CONCLUSION: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD. -
Publisher Correction: Identification of 371 genetic variants for age at first sex and birth linked to externalising behavior
No abstract -
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.
2020
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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... -
The role of polygenic risk and susceptibility genes in breast cancer over the course of life
Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer,... -
HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study
The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated ³H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial... -
Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3... -
Sex-specific associations of TCF7L2 variants with fasting glucose, type 2 diabetes and coronary heart disease among Turkish adults
CONCLUSION: T allele homozygosity of two SNVs as well as the diplotype H1-/H1- reflects risk of diabetes primarily in men. Enhanced CHD risk is determined by the presence of diplotype H1-/H1- among nondiabetic participants. -
An expanded analysis framework for multivariate GWAS connects inflammatory biomarkers to functional variants and disease
Multivariate methods are known to increase the statistical power to detect associations in the case of shared genetic basis between phenotypes. They have, however, lacked essential analytic tools to follow-up and understand the biology underlying these associations. We developed a novel computational workflow for multivariate GWAS follow-up analyses, including fine-mapping and identification of the subset of traits driving associations (driver traits). Many follow-up tools require univariate... -
The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study
CONCLUSION: We conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDL(lipids) were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis. -
Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers¹. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs... -
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not... -
Relation of intraventricular conduction delay to risk of new-onset heart failure and structural heart disease in the general population
CONCLUSION: LBBB and non-specific IVCD were associated with more than three-fold risk of new-onset HF. Furthermore, LBBB was associated with novel SHD. Their presence should alert clinician even in subjects free from any known heart disease. -
Childhood and long-term dietary calcium intake and adult cardiovascular risk in a population with high calcium intake
CONCLUSIONS: Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood. -
The prognostic significance of T-wave inversion according to ECG lead group during long-term follow-up in the general population
CONCLUSIONS: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon. -
Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin... -
Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations
Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10^(-9), including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with... -
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting...
2019
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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. -
Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men
The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atherosclerosis, diabetes, or antihypertensive medication, mean age 48 years, using whole-body impedance cardiography and radial pulse wave analysis. MS was defined according to Alberti et al. 2009. Men and women with MS presented with corresponding elevations of systolic and diastolic blood pressure (10-14%,... -
Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects
Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood... -
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. -
Childhood Psychosocial Environment and Adult Cardiac Health: A Causal Mediation Approach
CONCLUSIONS: A favorable childhood environment is associated with more optimal cardiac structure and function in adulthood. After accounting for socioeconomic positions, adult health behaviors explain little of the associations. -
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... -
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... -
Liquorice ingestion attenuates vasodilatation via exogenous nitric oxide donor but not via β2-adrenoceptor stimulation
We examined the effect of liquorice ingestion on haemodynamic responses to exogenous nitric oxide donor (nitroglycerin) and β2-adrenoceptor agonist (salbutamol), and 11β-hydroxysteroid dehydrogenase activity, in 21 volunteers and 21 reference subjects. Haemodynamic data was captured before and after sublingual nitroglycerin (0.25 mg) and inhaled salbutamol (400 μg) during orthostatic challenge utilising radial pulse wave analysis and whole-body impedance cardiography. The recordings were... -
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... -
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10^(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and...
2018
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Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients
CONCLUSIONS: GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings. -
Interethnic analyses of blood pressure loci in populations of East Asian and European descent
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize... -
Coronary heart disease risk factor levels in eastern and western Finland from 1980 to 2011 in the cardiovascular risk in Young Finns study
CONCLUSIONS: Our sample of adult Finns aged 34-49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might... -
Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
BACKGROUND: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. -
Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper. -
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we... -
LDL cholesterol is associated with systemic vascular resistance and wave reflection in subjects naive to cardiovascular drugs
CONCLUSIONS: LDL-C is independently associated with BP via systemic vascular resistance and wave reflection. These results suggest that LDL-C may play a role in the pathogenesis of primary hypertension. -
Impact of Ideal Cardiovascular Health in Childhood on the Retinal Microvasculature in Midadulthood: Cardiovascular Risk in Young Finns Study
Background This study examined the association between ideal cardiovascular health ( CVH ) and the retinal microvasculature in midadulthood. Methods and Results The Cardiovascular Risk in Young Finns Study included children from 5 Finnish University cities, who were chosen randomly from the national population register. Participants ranged from 12 to 18 years in childhood (1986) and from 37 to 43 years in midadulthood (2011). Ideal CVH was defined according to the American Heart Association... -
The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality
CONCLUSIONS: The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor. -
Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations
Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in... -
Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study
α-melanocyte-stimulating hormone (α-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. α-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and α-MSH expression in atherosclerosis. First, transcript levels of POMC and its processing enzymes were analyzed in human arterial plaques (n = 68) and non-atherosclerotic controls (n = 24)... -
Uncovering the complex genetics of human character
Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of... -
Uncovering the complex genetics of human temperament
Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions... -
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits
High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify... -
Effect of present versus previous smoking on non-invasive haemodynamics
We examined cardiovascular function in 637 volunteers (19-72 years) without antihypertensive medication in never smokers (n = 365), present smokers (n = 81) and previous smokers (n = 191, median abstinence 10 years). Haemodynamics during passive head-up tilt were recorded using whole-body impedance cardiography and radial pulse wave analysis. Results were adjusted for age, sex, body mass index, LDL cholesterol and alcohol use. Systolic and diastolic blood pressure, heart rate, and pulse wave...