Repeat Elements and Novel Genes Contribute to Sex-Specific Mechanisms of Metabolism

Obesity-associated mortality is exacerbated by high abdominal obesity. Here, we identify genes associated with obesity and waist-to-hip ratio adjusted for body mass index (WHRadjBMI), and allele-sensitive enhancers which are predicted to regulate female WHRadjBMI genes. 76% (45/59) of obesity and waist-to-hip ratio-associated variants are located in primate-specific Alu elements which contain a motif associated with adipocyte differentiation. SNX10, the strongest female WHRadjBMI-associated gene, is required for adipocyte differentiation and is required for adipose expansion in female mice, but not males, and the lead variant at the SNX10 locus affects intracellular lipids in human adipocytes. In conclusion, we find novel genes and a system of gene regulatory elements which regulate adipocyte differentiation and may affect human health.