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

To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI),...

Authors:
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Anderson D, et al.

Authors notes:
Nature. 2015;518(7538):197-206.

Keywords:
obesity susceptibility, genome-wide, loci, body mass index, BMI, new genes, glutamate signalling, insulin, energy metabolism, lipid, adipogenesis, GWAS, meta-analysis, genome-wide association study, Metabochip meta-analysis

Abstract:
Obesity is heritable and predisposes to many diseases.

To understand the genetic basis of obesity better, here we conduct 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.

This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel.

Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes.

The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation.

Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.