LAUSR

DNA exome sequencing at scale reveals unknown human biology of adiposity Obesity is a common disorder with major adverse effects on morbidity and mortality. Genetic factors play an important role in determining the extent to which people acquire energy and store it as fat, which has implications for the risk of developing obesity. Studies in patients with severe early-onset obesity have identified mutations in >20 genes that have a large effect on body mass index (BMI) (1), whereas genome-wide association studies (GWASs) in large populations have identified hundreds of common variants with more-subtle effects (2). On page 73 of this issue, Akbari et al. (3) report rare genetic variants influencing BMI identified through whole-exome sequencing of >600,000 people from the United Kingdom, the United States, and Mexico. The authors identified genes in which rare nonsynonymous variants were associated with either higher or lower BMI, bringing insight to the genetics underlying human adiposity.