Publications
2026
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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... -
Author Correction: Obesity rise plateaus in developed nations and accelerates in developing nations
No abstract -
Obesity as a risk factor for multimorbidity: a 23-years population-based prospective study
CONCLUSION: This 23-year study highlights midlife obesity as a risk factor for multimorbidity in later life. -
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. -
Type 2 diabetes and diabetic retinopathy in Finland during 2000-2017 based on nationwide survey and register data
CONCLUSIONS: The prevalence of type 2 diabetes has increased during the 2000s, which can be explained by the improved screening and unfavourable changes in lifestyle. However, the incidence of DR has decreased among type 2 diabetes patients, indicating the successful development and effectiveness of screening and therapies for both diabetes and DR. -
Usher syndrome-related visual impairment in Finland: A 35-year nationwide register-based study (1985-2019)
CONCLUSION: As the first nationwide, long-term register-based study of USH-related VI, this 35-year analysis demonstrates stable incidence alongside increasing prevalence, with an observed redistribution of registered VI severity away from Near-Total Blindness and Total Blindness. These findings reflect both the expected natural disease course and broader system-level influences on registration patterns, underscoring the value of long-term register data for monitoring rare disease epidemiology... -
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. -
Scalable biological-cognitive profiling for Alzheimer's disease in the population
Plasma phosphorylated tau217 has been suggested as a core biomarker for establishing a biological Alzheimer's disease diagnosis. This blood biomarker has not been studied together with scalable cognitive assessment tools in population-based samples. We investigated the prevalence of cognitive and Alzheimer's disease biomarker abnormalities and associations between plasma phosphorylated tau217 and remotely measured cognitive function in individuals without dementia. We used a population-based... -
Impact of delayed appointments on treatment outcomes in neovascular macular degeneration
CONCLUSIONS: Delays in anti-VEGF injections are common and strongly associated with vision loss. Therefore, it is important to improve patient awareness and compliance. Use of new longer-acting therapies may support this process. -
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... -
Evaluation of Genetics in the Association Between Cardiorespiratory Fitness and Health: Insights from a Genome-Wide Polygenic Score for Cardiorespiratory Fitness in the FinnGen and HUNT cohorts
We evaluated how much cardiorespiratory fitness (CRF)-related genetics contribute to the risk of common noncommunicable diseases (NCDs) and mortality, and whether individuals with different levels of CRF and genetic predispositions differ in health characteristics. We used a validated SBayesR-based genome-wide polygenic score, leveraging information from 905 707 single-nucleotide polymorphisms, to measure CRF genetics (PGS CRF). Associations with register-based incident NCDs and mortality were... -
Incidence, risk factors, and mortality impact of chronic kidney disease in middle-aged Finns: a 22-year population-based cohort study
BACKGROUND: Although many studies have estimated the prevalence of chronic kidney disease (CKD) in the general population, few have assessed its cumulative incidence over a long time using both estimated glomerular filtration rate (eGFR) and albuminuria or assessed how CKD occurrence influences mortality. METHODS: This prospective, population-based cohort study included 1144 Finnish participants aged 40–65 years at baseline, who were followed from 1996 to 2019. The study assessed the prevalence... -
Genetic architecture of lumbar spinal stenosis
Lumbar spinal stenosis (LSS) affects over 100 million people globally, with an increasing incidence due to an ageing population. While LSS is known to be heritable, its genetic basis remains poorly understood. We conduct a genome-wide meta-analysis of LSS in 40,303 cases and 741,469 controls. We identify 73 previously unreported loci in addition to 15 known loci, and highlight spinal degeneration as a key pathogenic mechanism. In 12,784 surgically treated cases, we discover five loci... -
Quantifying risk modifiers of hereditary hemochromatosis using genomic and electronic health record data
CONCLUSIONS: We demonstrated that use of large-scale electronic health record data allows for precise quantification of individual-level risk, which we present as risk tables to support clinical practice. Furthermore, our findings suggest that hemochromatosis may be under-recognized in Finland. -
Direct and indirect costs associated with declining distance visual acuity: A nationwide longitudinal cost-of-illness study with 11-year follow-up
CONCLUSION: In total, 7.6% of the national direct health care costs were attributed to declining VA, highlighting the savings potential if the prevalence of declining VA could be reduced. -
Altered tear fluid protein expression in persons with mild cognitive impairment
BackgroundTear fluid (TF) is a protein-rich fluid reported to reflect pathophysiological changes in several neurodegenerative diseases, including Alzheimer's disease. TF proteins are increasingly being considered as putative biomarker candidates to help in the diagnosis of disease. However, little information is available on TF protein changes in persons with mild cognitive impairment (MCI).ObjectiveThis study aimed to determine alterations in the expression of proteins in TF collected from...
2025
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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. -
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. -
A comparison of anthropometric indicators in predicting the incidence of diabetes and intermediate hyperglycaemia in Finland: a 22-year observational study
CONCLUSIONS: Alternative anthropometric indicators offer comparable predictive value and show potential for individualised type 2 diabetes and IH risk assessment. Sex-specific cutoffs and a multi-indicator approach could be used to improve screening and early intervention strategies, potentially improving public health management of diabetes risk. -
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... -
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. -
Neuroinflammation Markers in Tear Fluid of Mild Alzheimer's Disease
The protein composition of tear fluid (TF) reflects the severity and progression of many age-related diseases. Here, we evaluated TF proteins from patients with mild Alzheimer's disease (AD) and cognitively healthy controls (CO) to explore potential new biomarker molecules. The aim of this study was to explore potential new biomarker molecules by examining the expression of TF proteins whose function is related to neuroinflammation. We examined 53 participants (34 COs, mean age 71 years,... -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Altered tear fluid protein expression in persons with mild Alzheimer's disease in proteins involved in oxidative stress, protein synthesis, and energy metabolism
BackgroundTear fluid (TF) is a protein-rich solution that reflects pathophysiological changes in Alzheimer's disease (AD).ObjectiveIn this study, we examined whether TF proteins were differently expressed in persons with mild AD dementia compared to cognitively healthy controls (CO).MethodsWe analyzed data from 53 study participants including 34 CO (mean age, 71 years; Mini-Mental State Examination [MMSE] score, 28.9 ± 1.4), and 19 patients with AD (Clinical Dementia Rating, 0.5-1; mean age, 72... -
Prevalence and associated factors of reduced visual acuity and undercorrected refractive error in Finland: Results from a nationwide survey
CONCLUSION: Reduced VA is associated with socio-demographic disadvantage and unfavourable lifestyle. Two out of three persons with reduced VA do not have their spectacles up to date. Inadequately corrected refraction seems to be a complicated phenomenon related to several factors deserving further study. -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
Correction: Price tag of glaucoma care is minor compared with the total direct and indirect costs of glaucoma: Results from nationwide survey and register data
[This corrects the article DOI: 10.1371/journal.pone.0295523.]. -
First-line glaucoma monotherapy medication patterns in Finland during 1995-2019 based on a population-based study
CONCLUSIONS: During the 25-year follow-up a shift from beta-blockers to prostaglandin analogues had occurred and long initial therapies of over 5 years had become more common. However, the decline in the continuation of the initial therapy still occurred early with 1 out of 3 patients continuing after 3 years. This decline together with the consistent problem of non-persistence remain clinical challenges in topical drug therapy of glaucoma. -
Impact of signs and symptoms of dry eye disease on health-related quality of life: a cross-sectional population study among older adults
CONCLUSION: This first population-based study assessing general QoL data with objective clinical measures of DED indicated that among elderly population, both symptoms and signs of DED independently impacted different aspects of QoL. In addition, significant sex-differences in these associations were observed and should be considered both in research settings and when assessing and treating people with DED. -
Societal costs of decreased visual acuity: A Finnish cohort study with 15 years of registry data follow-up
CONCLUSIONS: In addition to those with visual impairment or blindness, health care need, and societal costs are elevated even among those with adequate VA. We conclude, that focusing on prevention of VA decrease would not only help sustain the patients' quality of life but could also reduce the future societal costs. -
Neovascular age-related macular degeneration on three nationwide survey and register data in Finland during 2000-2017
CONCLUSION: Since nAMD is an increasing burden for public health with gender discrepancy and a detrimental impact on vision, we should better find patients who have a high risk of developing nAMD and try to optimise their preventive intervention. Once nAMD is developed, we should understand treatment and follow-up demands at the personalised level. The nationwide register data help us in those challenges. -
Genome-wide association study of anterior uveitis
CONCLUSION: We identified six anterior uveitis-associated loci, including three novel loci with genome-wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune-related disorders, providing a foundation for further research and potential therapeutic interventions. -
Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton
BackgroundNew biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.ObjectiveWe investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.MethodsWe analyzed the data of the 53 study... -
The incidence of visual impairment due to retinitis pigmentosa has declined in Finland over the last 40 years
CONCLUSION: The VI caused by RP in Finland has decreased. It develops at an older age than in the past. We hypothesize that this trend may be attributed to informed decisions by visually impaired persons to refrain from having offspring to prevent the transmission of hereditary mutations. The severity of VI due to RP has remained relatively unchanged. The incidence of HRD diagnoses has decreased, and the diagnosis occurs at an older age among men. -
Genetic Susceptibility to Acute Viral Bronchiolitis
CONCLUSIONS: Our results suggest that genetic variants in CDHR3 and GSDMB modulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV. Severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals, or it could be a marker of genetic predisposition to asthma.
2024
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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. -
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... -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
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,... -
Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton
BackgroundNew biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.ObjectiveWe investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.MethodsWe analyzed the data of the 53 study... -
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. -
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... -
Erectile dysfunction as a predictive indicator of asymptomatic diabetes and prediabetes
CONCLUSIONS: The symptoms of ED appear to be an early warning sign of existing DM and preDM and predict an increased risk of developing abnormal glucose metabolism in the future. -
Novel Human Induced Pluripotent Stem Cell-Based Model for Retinal Pigment Epithelial Cells to Reveal Possible Disease Mechanisms for Macular Degeneration in Pseudoxanthoma Elasticum
Pseudoxanthoma elasticum (PXE) is a rare metabolic disease with autosomal recessive inheritance. The manifestation in PXE is represented by retinal complications, pseudoxanthomas of the skin folding areas, and arterial calcification. The retinal complications are caused by the calcification of Bruch's membrane beneath retinal pigment epithelial cells (RPE) that can lead to retinal macular degeneration. The exact mechanism for the retinal pathophysiology is not known, and patients have variable... -
The incidence of visual impairment due to retinitis pigmentosa has declined in Finland over the last 40 years
CONCLUSION: The VI caused by RP in Finland has decreased. It develops at an older age than in the past. We hypothesize that this trend may be attributed to informed decisions by visually impaired persons to refrain from having offspring to prevent the transmission of hereditary mutations. The severity of VI due to RP has remained relatively unchanged. The incidence of HRD diagnoses has decreased, and the diagnosis occurs at an older age among men. -
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. -
Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer
While hundreds of cancer-associated long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still largely a mystery. An increasing number of lncRNAs are recognized to function in the cytoplasm, e.g., as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in prostate cancer (PCa). First, we interrogated the transcript structure of EPCART and... -
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). -
TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer's disease
INTRODUCTION: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and... -
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. -
Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women
CONCLUSION: Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness. -
Comparison of early changes in tear film protein profiles after small incision lenticule extraction (SMILE) and femtosecond LASIK (FS-LASIK) surgery
CONCLUSIONS: Our study showed that immediate changes in protein profiles after SMILE and FS-LASIK surgeries and differences between the methods are connected to inflammatory process, and the protein levels quickly return to the baseline within 1 month. The differences in protein profiles between the methods are probably associated with the different size of the epithelial wound induced. -
High-Resolution Genotyping of Formalin-Fixed Tissue Accurately Estimates Polygenic Risk Scores in Human Diseases
Formalin-fixed paraffin-embedded (FFPE) tissues stored in biobanks and pathology archives are a vast but underutilized source for molecular studies on different diseases. Beyond being the "gold standard" for preservation of diagnostic human tissues, FFPE samples retain similar genetic information as matching blood samples, which could make FFPE samples an ideal resource for genomic analysis. However, research on this resource has been hindered by the perception that DNA extracted from FFPE... -
Sex-specific genetic risks for adverse outcomes after coronary revascularization procedures
Men and women have differing risks of adverse events after revascularization procedures and these differences could be partially driven by genetics. We studied the sex-specific differences in associations of polygenic risk scores (PRSs) with atrial fibrillation (AF), ischaemic stroke (STR), intracranial haemorrhage (ICH), myocardial infarction (MI) and gastrointestinal haemorrhage (GIH) in coronary revascularization patients. The study cohort comprised 5561 and 17 578 revascularized women and... -
Nationwide and regional trends in distance and near visual acuities during 2000-2017 in Finland
CONCLUSION: During the past two decades, the overall vision level has improved among the adult population. This is explained mostly by a positive shift from lower to higher vision levels among older age groups, indicating that people live longer with good or adequate vision. This positive trend showed remarkable similarity throughout different regions in Finland, highlighting the importance of equal and accessible eye care throughout the country. -
Electrically Induced Blink for the Prevention of Ocular Symptoms and Blurred Vision in Patients With Acute Facial Nerve Palsy
Objectives: Facial nerve palsy causes blurred vision and ocular discomfort due to deficits in blinking and eye closure. The objective of this study was to determine whether eye-blinks could be elicited by electrical stimulation and whether electrically induced blink would have an effect on the visual acuity and ocular symptoms in patients with acute facial nerve palsy. Methods: The zygomatic branch of the facial nerve of fifteen participants with acute facial nerve palsy was electrically...
2023
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Impact of delayed appointments on treatment outcomes in neovascular macular degeneration
CONCLUSIONS: Delays in anti-VEGF injections are common and strongly associated with vision loss. Therefore, it is important to improve patient awareness and compliance. Use of new longer-acting therapies may support this process. -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
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. -
Price tag of glaucoma care is minor compared with the total direct and indirect costs of glaucoma: Results from nationwide survey and register data
CONCLUSION: Glaucoma is associated with an increased health care consumption mainly due to non-eye-related health care, which can be explained by the vision loss as well as increased number of co-morbidities among glaucoma patients. Therefore, glaucoma constitutes a major economic burden for the health care system and society, highlighting the importance of early glaucoma interventions. The difference in direct and indirect costs between glaucoma treatment groups is explained by the uneven... -
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... -
Association of APOE Haplotypes With Common Age-Related Ocular Diseases in 412,171 Individuals
CONCLUSIONS: Our results support prior evidence of the inverse association of APOE ε4 with glaucoma, but the association was weaker than for AMD. We could not show an association with exfoliation glaucoma, supporting the hypothesis that APOE may be involved in regulating retinal ganglion cell degeneration rather than intraocular pressure. -
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... -
Nationwide and regional trends in distance and near visual acuities during 2000-2017 in Finland
CONCLUSION: During the past two decades, the overall vision level has improved among the adult population. This is explained mostly by a positive shift from lower to higher vision levels among older age groups, indicating that people live longer with good or adequate vision. This positive trend showed remarkable similarity throughout different regions in Finland, highlighting the importance of equal and accessible eye care throughout the country. -
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.... -
Data Resource Profile: Nationwide registry data for high-throughput epidemiology and machine learning (FinRegistry)
No abstract -
Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals
Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the... -
The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections
BACKGROUND: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor to respiratory infections. -
Proteomics of Deep Cervical Lymph Nodes After Experimental Traumatic Brain Injury
Traumatic brain injury (TBI) damages the glymphatic-lymphatic system. We hypothesized that brain injury associated with trauma results in the enrichment of brain-relevant proteins in deep cervical lymph nodes (DCLNs), the end station of meningeal lymphatic vessels, and that some of these proteins will present mechanistic tissue biomarkers for TBI. Proteomes of rat DCLNs were investigated in the left DCLN (ipsilateral to injury) and right DCLN at 6.5 months after severe TBI induced by lateral... -
Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy
CONCLUSIONS AND RELEVANCE: The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms. -
Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study
CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy. -
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant... -
Proteomics Analysis of R-Ras Deficiency in Oxygen Induced Retinopathy
Small GTPase R-Ras regulates vascular permeability in angiogenesis. In the eye, abnormal angiogenesis and hyperpermeability are the leading causes of vision loss in several ischemic retinal diseases such as proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Oxygen-induced retinopathy (OIR) is the most widely used experimental model for these ischemic retinopathies. To shed more light on how the R-Ras regulates vascular permeability in... -
Impact of vision on generic health-related quality of life - A systematic review
The aim of the study was to provide an overview on the relation between vision and generic health-related quality of life (HRQoL) in general populations worldwide. We conducted a systematic review to identify articles that have evaluated the relation of binocularly measured distance visual acuity (VA) and HRQoL in adults at population level around the world. Used search terms were related to visual acuity, vision loss, visual impairment and HRQoL. We identified 780 articles, of which 12... -
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... -
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies.... -
Comparison of three health-related quality of life instruments in relation to visual acuity: EQ-5D, 15D, and EUROHIS-QOL8
CONCLUSION: All three instruments can be viable tools in evaluating the relation between vision and HRQoL. While 15D is preferred due to its wide coverage of dimensions, EQ-5D can be an equal alternative, as it has less respondent burden. The feasibility of EUROHIS-QOL8 on detecting differences between lower VA levels may require further evidence. -
Visual impairment due to age-related macular degeneration during 40 years in Finland and the impact of novel therapies
CONCLUSION: Increase in the incidence and prevalence of VI due to AMD in the past decades has stagnated and shifted to older age in the 2010s when therapies for exudative class became commonly available. Furthermore, the prognosis of VI has improved during the past 40 years. These positive trends are likely contributable to improved diagnostic tools, earlier diagnoses, and new therapy options. -
Intraluminal deposits: A rare cause of glaucoma drainage implant total obstruction
CONCLUSIONS: Our study describes a new cause of total obstruction GDI tubes. The long-term use of timolol maleate and brinzolamide and their presence in the intraluminal solid sample collected from the blocked GDI tube suggest that the glaucoma medication may have a role in the pathogenesis. However, the exact mechanism is unknown and requires further studies.
2022
-
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
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. -
TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer's disease
INTRODUCTION: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and... -
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. -
Ocular surface disease signs and symptoms of glaucoma patients and their relation to glaucoma medication in Finland
CONCLUSION: Glaucoma patients show higher prevalence of OSD signs and dry eye sensation compared to non-glaucomatous population. The use of preserved glaucoma medication, as well as high number of active compounds and eye drops increase the severity of these parameters. There are significant differences between the types of glaucoma medication used, and therefore the selection of them is important especially in patients suffering from OSD. -
Comparison of three health-related quality of life instruments in relation to visual acuity: EQ-5D, 15D, and EUROHIS-QOL8
CONCLUSION: All three instruments can be viable tools in evaluating the relation between vision and HRQoL. While 15D is preferred due to its wide coverage of dimensions, EQ-5D can be an equal alternative, as it has less respondent burden. The feasibility of EUROHIS-QOL8 on detecting differences between lower VA levels may require further evidence. -
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. -
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... -
Visual impairment due to age-related macular degeneration during 40 years in Finland and the impact of novel therapies
CONCLUSION: Increase in the incidence and prevalence of VI due to AMD in the past decades has stagnated and shifted to older age in the 2010s when therapies for exudative class became commonly available. Furthermore, the prognosis of VI has improved during the past 40 years. These positive trends are likely contributable to improved diagnostic tools, earlier diagnoses, and new therapy options. -
Clinical Tear Fluid Proteomics-A Novel Tool in Glaucoma Research
Tear fluid forms the outermost layer of the ocular surface and its characteristics and composition have been connected to various ocular surface diseases. As tear proteomics enables the non-invasive investigation of protein levels in the tear fluid, it has become an increasingly popular approach in ocular surface and systemic disease studies. Glaucoma, which is a set of multifactorial diseases affecting mainly the optic nerve and retinal ganglion cells, has also been studied using tear... -
Elevated One-Hour Post-Load Glucose Is Independently Associated with Albuminuria: A Cross-Sectional Population Study
The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0... -
Changes in Visual Impairment due to Diabetic Retinopathy During 1980-2019 Based on Nationwide Register Data
CONCLUSIONS: Prevalence and incidence of VI due to DR have dramatically decreased and shifted to older age during the 40 years despite the increasing prevalence of diabetes. These positive trends highlight the successful development and effectiveness of screening and therapies for diabetes and DR. -
Antibacterial and Oxidative Stress-Protective Effects of Five Monoterpenes from Softwood
Volatile organic compounds (VOC) affect the quality of indoor air. Terpenes and especially monoterpenes are the main molecules emitted from softwood material (coniferous species), which is widely used in construction. The corneal epithelium is one of the first human membranes to encounter VOCs in the air. Moreover, the industrial use of pleasant-scented monoterpenes in cosmetics, food, and detergents exposes people to monoterpenes in their daily lives. In the present study, the health effective... -
Intraluminal deposits: A rare cause of glaucoma drainage implant total obstruction
CONCLUSIONS: Our study describes a new cause of total obstruction GDI tubes. The long-term use of timolol maleate and brinzolamide and their presence in the intraluminal solid sample collected from the blocked GDI tube suggest that the glaucoma medication may have a role in the pathogenesis. However, the exact mechanism is unknown and requires further studies. -
Various vascular malformations are prevalent in Finnish pseudoxanthoma elasticum (PXE) patients: a national registry study
CONCLUSIONS: The prevalence of diagnosed PXE appears to be lower in Finland than in estimates from other countries. Decreased visual acuity is the most prevalent complication. We suggest that various vascular malformations may be an unrecognized feature of PXE. -
Prevalence and 11-Year Incidence of Cataract and Cataract Surgery and the Effects of Socio-Demographic and Lifestyle Factors
CONCLUSION: The prevalence of cataract and cataract surgery is increasing with the ageing of the population. The increase in cataract surgery is likely also reflecting the improvements in eye care. The possibility to equally use health-care services throughout a country can reduce the impact of socio-demographic status. Healthy lifestyle delays the development of cataract, whereas smoking and high alcohol consumption are associated with earlier cataract development. Therefore, the availability... -
A Natural History of Erectile Dysfunction in Elderly Men: A Population-Based, Twelve-Year Prospective Study
There is a wide variation in the development and course of erectile dysfunction (ED) in men, which confirms the need for prospective studies. We conducted a cross-sectional analysis among the general male population at the baseline (n = 359) and in a follow-up survey (n = 218) 12 years later. The prospective 12-year study included 189 men. ED was assessed using the International Index of Erectile Function questionnaire. The mean age of the participants was 62.0 years at the baseline, while at... -
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted... -
Ocular surface health of the Finnish elderly population
CONCLUSION: Signs of OSD and DE are common among the Finnish elderly population. However, the diagnosis is affected by the diagnostic criteria used and significant differences exist between sexes. Although women were more frequently diagnosed with DE and OSD and experienced more ocular surface irritation, men had more often lid and meibomian gland-related issues. The current diagnostic criteria of DE pose a risk of misclassifying men, who commonly display less severe symptoms in comparison with... -
Integration of questionnaire-based risk factors improves polygenic risk scores for human coronary heart disease and type 2 diabetes
Large-scale biobank initiatives and commercial repositories store genomic data collected from millions of individuals, and tools to leverage the rapidly growing pool of health and genomic data in disease prevention are needed. Here, we describe the derivation and validation of genomics-enhanced risk tools for two common cardiometabolic diseases, coronary heart disease and type 2 diabetes. Data used for our analyses include the FinnGen study (N = 309,154) and the UK Biobank project (N = 343,672).... -
Looking deeper into ocular surface health: an introduction to clinical tear proteomics analysis
Ocular surface diseases are becoming more prevalent worldwide. Reasons for this include the ongoing population ageing and increasing use of digital displays, although ophthalmologists have a wide selection of tools, which can be implemented in the evaluation of the ocular surface health, methods, which enable the in-depth study of biological functions are gaining more interest. These new approaches are needed, since the individual responses to ocular surface diseases and treatments can vary from... -
Changes in incidence and severity of visual impairment due to glaucoma during 40 years - a register-based study in Finland
CONCLUSION: The incidence of reported VI due to glaucoma has increased during the 40 years, but the risk of treated glaucoma patients becoming visually impaired has decreased. Visual impairment (VI) also occurs at an older age. This is likely due to the earlier diagnoses and improved therapy. To prevent the unfavourable development of VI due to glaucoma among the ageing population in the future, all attempts need to be made to improve glaucoma care. -
Improving health-related quality of life in glaucoma during 11 years and its association with vision loss and treatment of the disease
CONCLUSION: Glaucoma patients show reduced HRQoL and mental health, which is associated with vision loss regardless of the awareness or treatment of the disease. However, this effect seems to be diminishing over time, and the newly diagnosed glaucoma did not show a significant effect on either HRQoL or mental health.
2021
-
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
Sex-specific genetic risks for adverse outcomes after coronary revascularization procedures
Men and women have differing risks of adverse events after revascularization procedures and these differences could be partially driven by genetics. We studied the sex-specific differences in associations of polygenic risk scores (PRSs) with atrial fibrillation (AF), ischaemic stroke (STR), intracranial haemorrhage (ICH), myocardial infarction (MI) and gastrointestinal haemorrhage (GIH) in coronary revascularization patients. The study cohort comprised 5561 and 17 578 revascularized women and... -
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. -
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted... -
Looking deeper into ocular surface health: an introduction to clinical tear proteomics analysis
Ocular surface diseases are becoming more prevalent worldwide. Reasons for this include the ongoing population ageing and increasing use of digital displays, although ophthalmologists have a wide selection of tools, which can be implemented in the evaluation of the ocular surface health, methods, which enable the in-depth study of biological functions are gaining more interest. These new approaches are needed, since the individual responses to ocular surface diseases and treatments can vary from... -
Electrically Induced Blink for the Prevention of Ocular Symptoms and Blurred Vision in Patients With Acute Facial Nerve Palsy
Objectives: Facial nerve palsy causes blurred vision and ocular discomfort due to deficits in blinking and eye closure. The objective of this study was to determine whether eye-blinks could be elicited by electrical stimulation and whether electrically induced blink would have an effect on the visual acuity and ocular symptoms in patients with acute facial nerve palsy. Methods: The zygomatic branch of the facial nerve of fifteen participants with acute facial nerve palsy was electrically... -
22-year trends in dysglycemia and body mass index: A population-based cohort study in Savitaipale, Finland
CONCLUSIONS: In this 22-year prospective follow-up study of in middle-aged Europeans with high participation rates, the progression of dysglycaemia to overt diabetes with aging was rapid, even without a significant change in BMI. -
Changes in incidence and severity of visual impairment due to glaucoma during 40 years - a register-based study in Finland
CONCLUSION: The incidence of reported VI due to glaucoma has increased during the 40 years, but the risk of treated glaucoma patients becoming visually impaired has decreased. Visual impairment (VI) also occurs at an older age. This is likely due to the earlier diagnoses and improved therapy. To prevent the unfavourable development of VI due to glaucoma among the ageing population in the future, all attempts need to be made to improve glaucoma care. -
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. -
Deep Bayesian baseline for segmenting diabetic retinopathy lesions: Advances and challenges
Early diagnosis of retinopathy is essential for preventing retinal complications and visual impairment due to diabetes. For the detection of retinopathy lesions from retinal images, several automatic approaches based on deep neural networks have been developed in the recent years. Most of the proposed methods produce point estimates of pixels belonging to the lesion areas and give no or little information on the uncertainty of method predictions. However, the latter can be essential in the... -
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. -
Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection
Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from... -
Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population
CONCLUSIONS AND RELEVANCE: This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population. -
Improving health-related quality of life in glaucoma during 11 years and its association with vision loss and treatment of the disease
CONCLUSION: Glaucoma patients show reduced HRQoL and mental health, which is associated with vision loss regardless of the awareness or treatment of the disease. However, this effect seems to be diminishing over time, and the newly diagnosed glaucoma did not show a significant effect on either HRQoL or mental health. -
Reduced evoked activity and cortical oscillations are correlated with anisometric amblyopia and impairment of visual acuity
Amblyopia is a developmental disorder associated with abnormal visual experience during early childhood commonly arising from strabismus and/or anisometropia and leading to dysfunctions in visual cortex and to various visual deficits. The different forms of neuronal activity that are attenuated in amblyopia have been only partially characterized. In electrophysiological recordings of healthy human brain, the presentation of visual stimuli is associated with event-related activity and oscillatory... -
Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL... -
One-year Results of Health-related and Vision-related Quality of Life After Clear Lens Extraction and Multifocal Intraocular Lens Implantation
CONCLUSIONS: CLE and MIOL implantation improved HRQoL and VRQoL compared to spectacles in this 1-year follow-up study. Improvement of HRQoL was correlated with VRQoL. -
Prevalence and 11-year incidence of common eye diseases and their relation to health-related quality of life, mental health, and visual impairment
CONCLUSION: Declined HRQoL associated with eye diseases is more related to impaired vision than the awareness of the disease itself, and this declining effect diminished during the follow-up. Therefore, information directed to the public on the risks and prevention of blindness can and should be strengthened to prevent the deleterious effects of visual impairment. -
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... -
Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants... -
Sleep apnoea is a risk factor for severe COVID-19
CONCLUSION: Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19. -
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... -
Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future
The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications... -
The effect of successful trabeculectomy on the ocular surface and tear proteomics-a prospective cohort study with 1-year follow-up
CONCLUSION: Clinical signs as well as the proteomics results indicated that the trabeculectomy and resulting cessation of topical glaucoma medication were very beneficial to the ocular surface. The state of the conjunctiva improved throughout the 1-year follow-up while the levels of pro-inflammatory proteins decreased and lipid transport-associated functions were increased.
2020
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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. -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer
While hundreds of cancer-associated long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still largely a mystery. An increasing number of lncRNAs are recognized to function in the cytoplasm, e.g., as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in prostate cancer (PCa). First, we interrogated the transcript structure of EPCART and... -
Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy
CONCLUSIONS AND RELEVANCE: The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms. -
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... -
Changes in Visual Impairment due to Diabetic Retinopathy During 1980-2019 Based on Nationwide Register Data
CONCLUSIONS: Prevalence and incidence of VI due to DR have dramatically decreased and shifted to older age during the 40 years despite the increasing prevalence of diabetes. These positive trends highlight the successful development and effectiveness of screening and therapies for diabetes and DR. -
Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population
CONCLUSIONS AND RELEVANCE: This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population. -
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,... -
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. -
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... -
Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future
The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications... -
Early changes in tear film protein profiles after femtosecond LASIK surgery
CONCLUSIONS: The present study showed that an uneventful femtosecond LASIK refractive surgery induced a significant immune cell migration and inflammation-associated changes in tear proteomics profile quickly after the operation, but the expression of most proteins recovered almost completely to the preoperative levels within the first month. The individual proteins identified in our study are potential targets for the follow-up and modification of LASIK-induced biochemical processes. -
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... -
Comparison of Capillary and Schirmer Strip Tear Fluid Sampling Methods Using SWATH-MS Proteomics Approach
CONCLUSIONS: Tear proteomics data originating from the same participants vary depending on whether the sample is collected with capillary or Schirmer strip, although there is also overlap between the two sample types when a combined spectral library is implemented in the SWATH-MS analysis. In discovery-based proteomics research of tear fluid, appropriate sampling method should be chosen carefully based on the research focus. -
In vitro stem cell modelling demonstrates a proof-of-concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy
Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disease of the macula that leads to bilateral loss of central vision and is caused by mutations in the TIMP3 gene. However, the mechanisms by which TIMP3 mutations cause SFD are poorly understood. Here, we generated human induced pluripotent stem cell-derived retinal pigmented epithelial (hiPSC-RPE) cells from three SFD patients carrying TIMP3 p.(Ser204Cys) and three non-affected controls to study disease-related structural and... -
The effect of successful trabeculectomy on the ocular surface and tear proteomics-a prospective cohort study with 1-year follow-up
CONCLUSION: Clinical signs as well as the proteomics results indicated that the trabeculectomy and resulting cessation of topical glaucoma medication were very beneficial to the ocular surface. The state of the conjunctiva improved throughout the 1-year follow-up while the levels of pro-inflammatory proteins decreased and lipid transport-associated functions were increased. -
Bioactive Properties of the Aqueous Extracts of Endophytic Fungi Associated with Scots Pine (Pinus sylvestris) Roots
Despite the continuing interest in various plant and natural products, only a small portion of the biologically active compounds from nature has been discovered and exploited. In this study, antioxidant and antibacterial properties of aqueous fractions of three endophytic fungi isolated from the roots of 8-year-old Scots pines (Pinus sylvestris) growing on a drained peatland were investigated. The endophytic fungi species were Acephala applanata, Phialocephala fortinii, and Humicolopsis... -
Repositioning of the global epicentre of non-optimal cholesterol
High blood cholesterol is typically considered a feature of wealthy western countries^(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world³ and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health^(4,5). However, the trends of HDL and non-HDL cholesterol... -
Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration
Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. The ubiquitin-proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is... -
Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers
Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases^(1-3). We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease... -
Correlation between the rate of intravitreal injections, use of aflibercept as a second-line treatment and visual impairment for wet AMD in Finland
CONCLUSION: These results emphasize that the use of aflibercept injections as a second-line treatment may decrease new onset visual impairments. -
Comparing glaucoma medications and general demographics in a sample of glaucoma patients treated in private practice with nationwide registry data in Finland
CONCLUSION: The study patients were treated effectively by private ophthalmologist. Their medication and the cost of medication were the same as in public clinics. Patients with aggressive glaucoma seem to be generally managed by public hospitals. -
National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio: a pooled analysis of 458 population-based studies in Asian and Western countries
CONCLUSIONS: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol. -
Patient satisfaction and self-reported dry eye symptoms in hyperopic patients treated with femtosecond laser in situ keratomileusis
CONCLUSION: FS-LASIK correction of hyperopia significantly improved patient satisfaction with both near and far vision in monovision patients. Hyperopic patients had no significant changes in postoperative dry eye symptoms compared to preoperative values. -
Uncorrected visual acuity, postoperative astigmatism, and dry eye symptoms are major determinants of patient satisfaction: a comparative, real-life study of femtosecond laser in situ keratomileusis and small incision lenticule extraction for myopia
CONCLUSIONS: In a real-life situation, patients with preoperative dry eye experience were often directed to the SMILE operation, which resulted in beneficial decrease in their dry eye symptoms. Patient satisfaction with far vision decreased with increasing dry eye symptoms and postoperative astigmatism in both SMILE- and FS-LASIK-treated emmetropic patients. Safety, efficacy, and predictability were comparable in both treatments.
2019
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Usher syndrome-related visual impairment in Finland: A 35-year nationwide register-based study (1985-2019)
CONCLUSION: As the first nationwide, long-term register-based study of USH-related VI, this 35-year analysis demonstrates stable incidence alongside increasing prevalence, with an observed redistribution of registered VI severity away from Near-Total Blindness and Total Blindness. These findings reflect both the expected natural disease course and broader system-level influences on registration patterns, underscoring the value of long-term register data for monitoring rare disease epidemiology... -
Incidence, risk factors, and mortality impact of chronic kidney disease in middle-aged Finns: a 22-year population-based cohort study
BACKGROUND: Although many studies have estimated the prevalence of chronic kidney disease (CKD) in the general population, few have assessed its cumulative incidence over a long time using both estimated glomerular filtration rate (eGFR) and albuminuria or assessed how CKD occurrence influences mortality. METHODS: This prospective, population-based cohort study included 1144 Finnish participants aged 40–65 years at baseline, who were followed from 1996 to 2019. The study assessed the prevalence... -
Direct and indirect costs associated with declining distance visual acuity: A nationwide longitudinal cost-of-illness study with 11-year follow-up
CONCLUSION: In total, 7.6% of the national direct health care costs were attributed to declining VA, highlighting the savings potential if the prevalence of declining VA could be reduced. -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
First-line glaucoma monotherapy medication patterns in Finland during 1995-2019 based on a population-based study
CONCLUSIONS: During the 25-year follow-up a shift from beta-blockers to prostaglandin analogues had occurred and long initial therapies of over 5 years had become more common. However, the decline in the continuation of the initial therapy still occurred early with 1 out of 3 patients continuing after 3 years. This decline together with the consistent problem of non-persistence remain clinical challenges in topical drug therapy of glaucoma. -
Societal costs of decreased visual acuity: A Finnish cohort study with 15 years of registry data follow-up
CONCLUSIONS: In addition to those with visual impairment or blindness, health care need, and societal costs are elevated even among those with adequate VA. We conclude, that focusing on prevention of VA decrease would not only help sustain the patients' quality of life but could also reduce the future societal costs. -
The incidence of visual impairment due to retinitis pigmentosa has declined in Finland over the last 40 years
CONCLUSION: The VI caused by RP in Finland has decreased. It develops at an older age than in the past. We hypothesize that this trend may be attributed to informed decisions by visually impaired persons to refrain from having offspring to prevent the transmission of hereditary mutations. The severity of VI due to RP has remained relatively unchanged. The incidence of HRD diagnoses has decreased, and the diagnosis occurs at an older age among men. -
Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women
CONCLUSION: Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness. -
Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy
CONCLUSIONS AND RELEVANCE: The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms. -
Visual impairment due to age-related macular degeneration during 40 years in Finland and the impact of novel therapies
CONCLUSION: Increase in the incidence and prevalence of VI due to AMD in the past decades has stagnated and shifted to older age in the 2010s when therapies for exudative class became commonly available. Furthermore, the prognosis of VI has improved during the past 40 years. These positive trends are likely contributable to improved diagnostic tools, earlier diagnoses, and new therapy options. -
Changes in Visual Impairment due to Diabetic Retinopathy During 1980-2019 Based on Nationwide Register Data
CONCLUSIONS: Prevalence and incidence of VI due to DR have dramatically decreased and shifted to older age during the 40 years despite the increasing prevalence of diabetes. These positive trends highlight the successful development and effectiveness of screening and therapies for diabetes and DR. -
Antibacterial and Oxidative Stress-Protective Effects of Five Monoterpenes from Softwood
Volatile organic compounds (VOC) affect the quality of indoor air. Terpenes and especially monoterpenes are the main molecules emitted from softwood material (coniferous species), which is widely used in construction. The corneal epithelium is one of the first human membranes to encounter VOCs in the air. Moreover, the industrial use of pleasant-scented monoterpenes in cosmetics, food, and detergents exposes people to monoterpenes in their daily lives. In the present study, the health effective... -
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted... -
22-year trends in dysglycemia and body mass index: A population-based cohort study in Savitaipale, Finland
CONCLUSIONS: In this 22-year prospective follow-up study of in middle-aged Europeans with high participation rates, the progression of dysglycaemia to overt diabetes with aging was rapid, even without a significant change in BMI. -
Changes in incidence and severity of visual impairment due to glaucoma during 40 years - a register-based study in Finland
CONCLUSION: The incidence of reported VI due to glaucoma has increased during the 40 years, but the risk of treated glaucoma patients becoming visually impaired has decreased. Visual impairment (VI) also occurs at an older age. This is likely due to the earlier diagnoses and improved therapy. To prevent the unfavourable development of VI due to glaucoma among the ageing population in the future, all attempts need to be made to improve glaucoma care. -
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. -
Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population
CONCLUSIONS AND RELEVANCE: This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population. -
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. -
Comparing glaucoma medications and general demographics in a sample of glaucoma patients treated in private practice with nationwide registry data in Finland
CONCLUSION: The study patients were treated effectively by private ophthalmologist. Their medication and the cost of medication were the same as in public clinics. Patients with aggressive glaucoma seem to be generally managed by public hospitals. -
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... -
Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium
CONCLUSIONS: Taken together, our study shows that Na(v) channels are present in RPE, giving this tissue the capacity of fast electrical signaling. The channels are critical for the physiology of RPE with an important role in photoreceptor outer segment phagocytosis. -
Low vision status and declining vision decrease Health-Related Quality of Life: Results from a nationwide 11-year follow-up study
CONCLUSIONS: HRQoL was significantly and meaningfully impaired even before the threshold of severe vision loss or blindness was reached. The results encourage the improvement of available treatment options aiming to postpone the onset of visual impairment or declining VA, to maintain better quality of life among the population. -
Patient satisfaction and self-reported dry eye symptoms in hyperopic patients treated with femtosecond laser in situ keratomileusis
CONCLUSION: FS-LASIK correction of hyperopia significantly improved patient satisfaction with both near and far vision in monovision patients. Hyperopic patients had no significant changes in postoperative dry eye symptoms compared to preoperative values. -
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities^(1,2). This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity^(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or... -
Viability of Mouse Retinal Explant Cultures Assessed by Preservation of Functionality and Morphology
CONCLUSIONS: Retinal explants provide a valuable tool for studies of retinal functions and development of ocular therapies. However, critical for long-term use, retinal functionality was lost before structural loss, emphasizing a need for both functional and morphologic readouts to determine the overall state of the cultured retina. -
Age-associated changes in human tear proteome
CONCLUSIONS: Overall, the results show the common age-dependent alterations in tear fluid protein profile, which demonstrate similar age-associated alterations of biological functions previously shown in other tissue and sample types.
2018
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Incidence, risk factors, and mortality impact of chronic kidney disease in middle-aged Finns: a 22-year population-based cohort study
BACKGROUND: Although many studies have estimated the prevalence of chronic kidney disease (CKD) in the general population, few have assessed its cumulative incidence over a long time using both estimated glomerular filtration rate (eGFR) and albuminuria or assessed how CKD occurrence influences mortality. METHODS: This prospective, population-based cohort study included 1144 Finnish participants aged 40–65 years at baseline, who were followed from 1996 to 2019. The study assessed the prevalence... -
A comparison of anthropometric indicators in predicting the incidence of diabetes and intermediate hyperglycaemia in Finland: a 22-year observational study
CONCLUSIONS: Alternative anthropometric indicators offer comparable predictive value and show potential for individualised type 2 diabetes and IH risk assessment. Sex-specific cutoffs and a multi-indicator approach could be used to improve screening and early intervention strategies, potentially improving public health management of diabetes risk. -
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Biallelic loss-of-function variants in TYROBP and TREM2 cause autosomal recessive presenile dementia with bone cysts known as Nasu-Hakola disease (NHD, alternatively polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). Some other TREM2 variants contribute to the risk of Alzheimer's disease (AD) and frontotemporal dementia, while deleterious TYROBP variants are globally extremely rare and their role in neurodegenerative diseases remains unclear. The population... -
Narcolepsy as a potential risk factor for Schizophrenia
Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total... -
Impact of signs and symptoms of dry eye disease on health-related quality of life: a cross-sectional population study among older adults
CONCLUSION: This first population-based study assessing general QoL data with objective clinical measures of DED indicated that among elderly population, both symptoms and signs of DED independently impacted different aspects of QoL. In addition, significant sex-differences in these associations were observed and should be considered both in research settings and when assessing and treating people with DED. -
22-year trends in dysglycemia and body mass index: A population-based cohort study in Savitaipale, Finland
CONCLUSIONS: In this 22-year prospective follow-up study of in middle-aged Europeans with high participation rates, the progression of dysglycaemia to overt diabetes with aging was rapid, even without a significant change in BMI. -
Repositioning of the global epicentre of non-optimal cholesterol
High blood cholesterol is typically considered a feature of wealthy western countries^(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world³ and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health^(4,5). However, the trends of HDL and non-HDL cholesterol... -
Uncorrected visual acuity, postoperative astigmatism, and dry eye symptoms are major determinants of patient satisfaction: a comparative, real-life study of femtosecond laser in situ keratomileusis and small incision lenticule extraction for myopia
CONCLUSIONS: In a real-life situation, patients with preoperative dry eye experience were often directed to the SMILE operation, which resulted in beneficial decrease in their dry eye symptoms. Patient satisfaction with far vision decreased with increasing dry eye symptoms and postoperative astigmatism in both SMILE- and FS-LASIK-treated emmetropic patients. Safety, efficacy, and predictability were comparable in both treatments. -
Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia
Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This... -
Patient stratification in clinical glaucoma trials using the individual tear proteome
Glaucoma patients are prone to concomitant ocular surface diseases; however, switching from preserved to preservative-free medication can often alleviate these symptoms. The objective of this study was to examine how the adverse effects and tear proteome change for glaucoma patients (n = 28) during a 12-month drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost (Taflotan). We hypothesized that patient stratification could help identify novel recovery patterns in both... -
Comparison of iTRAQ and SWATH in a clinical study with multiple time points
CONCLUSIONS: Overall, we conclude that SWATH should be preferred for biomarker discovery studies when analyzing limited volumes of clinical samples collected at multiple time points. -
SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets
CONCLUSIONS: The results reveal new potential therapeutic targets to address hypoxia-induced pathological angiogenesis taking place in number of retinal diseases. The extensive proteomic profiling combined with pathway analysis also identifies novel molecular networks that could contribute to the pathogenesis of retinal diseases. -
Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants
CONCLUSIONS: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups. -
Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression
To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC,... -
Furin deficiency in myeloid cells leads to attenuated revascularization in a mouse-model of oxygen-induced retinopathy
Ischemic retinopathy is a vision-threatening disease associated with chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of angiogenesis due to its essential role in the activation of several angiogenic growth factors, including vascular endothelial growth factor-C (VEGF-C), VEGF-D and transforming growth factor - β (TGF- β). In the present study, we evaluated expression... -
Topical fluorometholone treatment and desiccating stress change inflammatory protein expression in tears
CONCLUSIONS: The identified proteins could be further used as biomarkers to identify patients most benefiting from FML treatment.