Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

Sara L Pulit, Charli Stoneman, Andrew P Morris, Andrew R Wood, Craig A Glastonbury, Jessica Tyrrell, Loïc Yengo, Teresa Ferreira, Eirini Marouli, Yingjie Ji, Jian Yang, Samuel Jones, Robin Beaumont, Damien C Croteau-Chonka, Thomas W Winkler, GIANT Consortium, Andrew T Hattersley, Ruth J F Loos, Joel N Hirschhorn, Peter M Visscher, Timothy M Frayling, Hanieh Yaghootkar, Cecilia M Lindgren

One in four adults worldwide are either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, is most informative for predicting risk of obesity sequellae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio adjusted for BMI (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.