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

Nature. 2015 Feb 12;518(7538):197-206. doi: 10.1038/nature14177.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adipogenesis / genetics
  • Adiposity / genetics
  • Age Factors
  • Body Mass Index*
  • Energy Metabolism / genetics
  • Europe / ethnology
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study*
  • Glutamic Acid / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Obesity / genetics*
  • Obesity / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics
  • Racial Groups / genetics
  • Synapses / metabolism

Substances

  • Insulin
  • Glutamic Acid

Grants and funding