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

Academic Article

Abstract

  • © 2015 Macmillan Publishers Limited. All rights reserved. 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.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Locke AE; Kahali B; Berndt SI; Justice AE; Pers TH; Day FR; Powell C; Vedantam S; Buchkovich ML; Yang J
  • Start Page

  • 197
  • End Page

  • 206
  • Volume

  • 518
  • Issue

  • 7538