Genetics of Obesity Traits: A Bivariate Genome-Wide Association Analysis

Previous genome-wide association studies on anthropometric measurements have identified more than 100 related loci, but only a small portion of heritability in obesity was explained. Here we present a bivariate twin study to look for the genetic variants associated with body mass index and waist-hip ratio, and to explore the obesity-related pathways in Northern Han Chinese. Cholesky decomposition model for 242 monozygotic and 140 dizygotic twin pairs indicated a moderate genetic correlation ( = 0.53, 95%CI: 0.42-0.64) between body mass index and waist-hip ratio. Bivariate genome-wide association analysis in 139 dizygotic twin pairs identified 26 associated SNPs with < 10 . Further gene-based analysis found 291 nominally associated genes ( < 0.05), including , and , as well as 6 enriched gene-sets with FDR < 0.05. Expression quantitative trait loci analysis identified rs2242044 as a significant cis-eQTL in both the normal adipose-subcutaneous ( = 1.7 × 10 ) and adipose-visceral ( = 4.4 × 10 ) tissue. These findings may provide an important entry point to unravel genetic pleiotropy in obesity traits.