Over 80% of African-American (AA) women are overweight or obese. A large racial disparity between AA and European-Americans (EA) in obesity rates exists among women, but curiously not among men. Although socio-economic and/or cultural factors may partly account for this race-by-sex interaction, the potential involvement of genetic factors has not yet been investigated. Among 2,814 self-identified AA in the Atherosclerosis Risk in Communities study, we estimated each individual’s degree of West-African genetic ancestry using 3,437 ancestry informative markers. We then tested whether sex modifies the association between West-African genetic ancestry and body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), adjusting for income and education levels, and examined associations of ancestry with the phenotypes separately in males and females. We replicated our findings in the Multi-Ethnic Study of Atherosclerosis (n=1,611 AA). In both studies, we find that West-African ancestry is negatively associated with obesity, especially central obesity, among AA men, but not among AA women (pinteraction= 1.24 x 10-5 in pooled analysis of WHR). In conclusion, our results suggest that the combination of male sex and West-African genetic ancestry is associated with protection against central adiposity, and suggest that the large racial disparity that exists among women, but not men, may be at least partly attributed to genetic factors
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