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Open AccessGenome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits
Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP...
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Article
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic a...
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Article
Open AccessExpression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study
Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs ...
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Open AccessGenetic insights into resting heart rate and its role in cardiovascular disease
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associate...
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Open AccessEvaluating the use of blood pressure polygenic risk scores across race/ethnic background groups
We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clum**-and-thresholding” (PRSice2) and LD-based (LD...
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Open AccessIntegrative Mendelian randomization reveals the soluble receptor for advanced glycation end products as protective in relation to rheumatoid arthritis
Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized ...
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Article
Open AccessMulti-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, who...
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Open AccessGenetic diversity fuels gene discovery for tobacco and alcohol use
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the...
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Article
Open AccessWhole genome DNA and RNA sequencing of whole blood elucidates the genetic architecture of gene expression underlying a wide range of diseases
To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene exp...
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Open AccessElucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease
DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trai...
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Article
Rare genetic variants explain missing heritability in smoking
Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contributio...
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Open AccessA multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood
In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is train...
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Open AccessDifferential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide associat...
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Article
Open AccessRare coding variants in RCN3 are associated with blood pressure
While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, geno...
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Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging
Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry g...
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Open AccessMeta-analyses identify DNA methylation associated with kidney function and damage
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledg...
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Open AccessEpigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures ...
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Article
Open AccessMeta-analysis of epigenome-wide association studies of carotid intima-media thickness
Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide ...
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Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00832-z.
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Open AccessGenome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification
Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression sign...
