Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men for six ectopic fat traits in European, African, Hispanic, and Chinese ancestry populations, with and without sex stratification. In total, 7 new loci were identified in association with ectopic fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P<5×10−8; FDR<1%). Functional analysis of these genes revealed that loss of function of both ATXN1 and UBE2E2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting a physiological role for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes impact adipocyte biology and how their perturbations contribute to systemic metabolic disease.
Chu, Audrey Y.; Deng, Xuan; Fisher, Virginia A.; Drong, Alexander; Zhang, Yang; Feitosa, Mary F.; Liu, Ching-Ti; Weeks, Olivia; Choh, Audrey C.; Duan, Qing; and Dyer, Thomas D., "Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation" (2017). School of Medicine Publications and Presentations. 118.
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