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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.

Original publication

DOI

10.1093/hmg/ddy327

Type

Journal article

Journal

Human molecular genetics

Publication Date

01/2019

Volume

28

Pages

166 - 174

Addresses

Big Data Institute, Li Ka Shing Center for Health Information and Discovery, Oxford University, Oxford, UK.

Keywords

Adipose Tissue, Humans, Obesity, Genetic Predisposition to Disease, Body Mass Index, Waist-Hip Ratio, Gene Frequency, Polymorphism, Single Nucleotide, Alleles, Adult, European Continental Ancestry Group, Female, Male, Adiposity, Body Fat Distribution, Genome-Wide Association Study