The genetics of obesity: from discovery to biology

In this Review, Loos and Yeo summarize our current understanding of the genetic underpinnings of monogenic and polygenic obesity. They highlight the commonalities revealed by recent studies and discuss the implications for treatment and prediction of obesity risk. 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.

Automated summary

In this review, Loos and Yeo summarize our current understanding of the genetic underpinnings of monogenic and polygenic obesity, highlighting shared genetic and biological underpinnings between the two forms of obesity. Genome-wide association studies with increasing sample sizes have driven recent discoveries, with post-GWAS collaborations facilitating translation of genetic loci into meaningful biology and new treatment avenues.