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Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14(More)
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of(More)
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of(More)
Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci(More)
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167(More)
Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype(More)
We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed(More)
Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown(More)
Several gastrointestinal (GI) operations that were designed to promote weight loss can powerfully ameliorate type 2 diabetes mellitus (T2DM). Although T2DM is traditionally viewed as a chronic, relentless disease in which delay of end-organ complications is the major treatment goal, GI surgery offers a novel endpoint: complete disease remission. Ample data(More)
Gastrointestinal weight-loss surgery (GIWLS) is currently the most effective treatment for severe obesity, with Roux en-Y gastric bypass (RYGB) among the best of the available surgical options. Despite its widespread clinical use, the mechanisms by which RYGB induces its profound weight loss remain largely unknown. This procedure effects weight loss by(More)