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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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Open AccessGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic c...
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Open AccessAuthor Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
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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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Open AccessGenetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative tra...
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Open AccessGenetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a...
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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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Open AccessA polygenic and family risk score are both independently associated with risk of type 2 diabetes in a population-based study
The availability of polygenic scores for type 2 diabetes (T2D) raises the question, whether assessing family history might become redundant. However, family history not only involves shared genetics, but also ...
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Open AccessNetwork reconstruction for trans acting genetic loci using multi-omics data and prior information
Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights i...
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Article
Open AccessA saturated map of common genetic variants associated with human height
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sa...
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Open AccessPublisher Correction: Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy
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Open AccessEpigenome-wide association study of incident type 2 diabetes: a meta-analysis of five prospective European cohorts
Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those ...
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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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Open AccessExtensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy
Clinical presentation of congenital heart disease is heterogeneous, making identification of the disease-causing genes and their genetic pathways and mechanisms of action challenging. By using in vivo electroc...
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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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Genetic insights into biological mechanisms governing human ovarian ageing
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 ...
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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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Open AccessMetabolic syndrome and the plasma proteome: from association to causation
The metabolic syndrome (MetS), defined by the simultaneous clustering of cardio-metabolic risk factors, is a significant worldwide public health burden with an estimated 25% prevalence worldwide. The pathogene...
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Open AccessAssociations between habitual diet, metabolic disease, and the gut microbiota using latent Dirichlet allocation
The gut microbiome impacts human health through various mechanisms and is involved in the development of a range of non-communicable diseases. Diet is a well-known factor influencing microbe-host interaction i...
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Open AccessRevealing the role of the human blood plasma proteome in obesity using genetic drivers
Blood circulating proteins are confounded readouts of the biological processes that occur in different tissues and organs. Many proteins have been linked to complex disorders and are also under substantial gen...
