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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Elizabeth K. Speliotes, +374 more
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TLDR
18 new loci associated with body mass index are identified, one of which includes a copy number variant near GPRC5B, and genes in other newly associated loci may provide new insights into human body weight regulation.
Abstract
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 approximately 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 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-)(8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

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LD score regression distinguishes confounding from polygenicity in genome-wide association studies :

TL;DR: It is found that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size, and the LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control.
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Genetic studies of body mass index yield new insights for obesity biology

TL;DR: A genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals provide strong support for a role of the central nervous system in obesity susceptibility.
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Richness of human gut microbiome correlates with metabolic markers

TL;DR: The authors' classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

Genetic studies of body mass index yield new insights for obesity biology

Adam E. Locke, +481 more
TL;DR: This paper conducted a genome-wide association study and meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals.
References
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TL;DR: The ProbABEL software package provides fast efficient way to analyze imputed data in genome-wide context and will facilitate future identification of complex trait loci.
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- 05 Aug 2010 -