The genetics of obesity: from discovery to biology

Nat Rev Genet. 2022 Feb;23(2):120-133. doi: 10.1038/s41576-021-00414-z. Epub 2021 Sep 23.

Abstract

The prevalence of obesity has tripled over the past four decades, imposing an enormous burden on people's health. Polygenic (or common) obesity and rare, severe, early-onset monogenic obesity are often polarized as distinct diseases. However, gene discovery studies for both forms of obesity show that they have shared genetic and biological underpinnings, pointing to a key role for the brain in the control of body weight. Genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology are the main drivers behind a recent flurry of new discoveries. However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate translation of genetic loci into meaningful biology and new avenues for treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Eating / genetics
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Genome, Human / genetics*
  • Genome-Wide Association Study / methods*
  • Humans
  • Multifactorial Inheritance / genetics
  • Obesity / genetics*
  • Overweight / genetics
  • Whole Genome Sequencing / methods*