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

Abstract

Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (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.

Keywords

Affiliated Institutions

• Brigham and Women's Hospital US
• Royal Devon & Exeter NHS Foundation Trust GB
• Harvard University US
• The University of Queensland AU
• Utrecht University NL
• Boston Children's Hospital US
• Health Data Research UK GB
• Centre for Human Genetics GB
• University of Regensburg DE
• University of Exeter GB
• William Harvey Research Institute GB
• Queen Mary University of London GB
• University of Liverpool GB
• Child Health and Development Institute US
• University Medical Center Utrecht NL
• University of Oxford GB
• Broad Institute US
• Icahn School of Medicine at Mount Sinai US

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