Genome-wide association studies of obesity and related traits

© 2014 S. Karger AG, Basel. Genome-wide association studies (GWAS) of obesity-related traits are defining the genetic architecture of obesity, revealing genes and mechanisms for disease. GWAS have been performed for several measures of obesity including body mass index (BMI), body fat distribution, and fat mass. Adults, adolescents, and children have been studied, as have populations of differing ancestries. At least 78 loci have been identified, 7 of which include one of the 59 genes implicated in monogenic forms of obesity or lipodystrophy. Nine of the obesity loci co-localise with type 2 diabetes GWAS signals. Genetic associations with body size tend to be similar in males and females, while many associations with body fat distribution have stronger effects in females. In addition to GWAS, analyses of copynumber variation have identified additional obesity variants and genes. Different types of genes appear to influence body size versus fat distribution. Many variants associated with body size are located near neuronal genes, such as those that affect appetite regulation, while many variants associated with fat distribution are located near genes that affect insulin signalling, fat deposition and metabolic traits. Future studies will identify additional loci, dissect pleiotropic relationships, and reveal additional underlying genes and biological mechanisms.