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Article
Open AccessUnderstanding the genetic complexity of puberty timing across the allele frequency spectrum
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, th...
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Article
Open AccessGWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on ‘around the clock’ glucoregula...
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Article
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin ac...
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Article
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the...
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Article
Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function
We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP–CpG associations (methylation quan...
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Article
The trans-ancestral genomic architecture of glycemic traits
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregate...
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Article
Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome
The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory1,2, neurologic3 and neoplastic diseases4. Recent genome-wide association studies yielded inconsistent, underpower...
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Article
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 22...
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Article
Fine-map** type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend th...
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Article
Refining the accuracy of validated target identification through coding variant fine-map** in type 2 diabetes
We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk...
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Article
Exome-wide association study of plasma lipids in >300,000 individuals
Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the eff...
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Article
Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
John Perry, Ken Ong and colleagues analyze genotype data on ∼370,000 women and identify 389 independent signals that associate with age at menarche, implicating ∼250 genes. Their analyses suggest causal invers...
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Article
Genetic fine map** and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci
Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine map** and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants i...
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Article
The impact of low-frequency and rare variants on lipid levels
Samuli Ripatti and colleagues report the results of a genome-wide association study for circulating lipid levels based on 1000 Genomes Project imputation. Their results implicate several new loci, refine the a...
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Article
Defining the role of common variation in the genomic and biological architecture of adult human height
Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci signif...
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Article
Genome-wide association analysis identifies six new loci associated with forced vital capacity
Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. The...
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Article
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of Europe...
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Article
Common variants associated with plasma triglycerides and risk for coronary artery disease
Sekar Kathiresan and colleagues examine 185 common variants using a modified mendelian randomization approach and provide evidence supporting a causal role of triglyceride-rich lipoproteins in the development ...
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Article
Systematic identification of trans eQTLs as putative drivers of known disease associations
Lude Franke and colleagues report the results of a large expression QTL study performed on peripheral blood samples from 5,311 individuals. They identify trans-eQTL effects for 103 independent loci that were prev...
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Article
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesit...