| Literature DB >> 27918534 |
Audrey Y Chu1,2, Xuan Deng3, Virginia A Fisher3, Alexander Drong4, Yang Zhang5,6, Mary F Feitosa7, Ching-Ti Liu3, Olivia Weeks6, Audrey C Choh8, Qing Duan9, Thomas D Dyer10, John D Eicher1, Xiuqing Guo11, Nancy L Heard-Costa3, Tim Kacprowski12,13, Jack W Kent14, Leslie A Lange9, Xinggang Liu15, Kurt Lohman16,17, Lingyi Lu17, Anubha Mahajan4, Jeffrey R O'Connell15, Ankita Parihar15, Juan M Peralta10, Albert V Smith18,19, Yi Zhang20, Georg Homuth12, Ahmed H Kissebah20, Joel Kullberg21, René Laqua22, Lenore J Launer23, Matthias Nauck13,24, Michael Olivier14,20, Patricia A Peyser25, James G Terry26, Mary K Wojczynski7, Jie Yao11, Lawrence F Bielak25, John Blangero10, Ingrid B Borecki7, Donald W Bowden27,28, John Jeffrey Carr26, Stefan A Czerwinski29, Jingzhong Ding16,30, Nele Friedrich13,24, Vilmunder Gudnason18,19, Tamara B Harris23, Erik Ingelsson31,32, Andrew D Johnson1, Sharon L R Kardia25, Carl D Langefeld17, Lars Lind21, Yongmei Liu16,33, Braxton D Mitchell15,34, Andrew P Morris4,35, Thomas H Mosley36, Jerome I Rotter11, Alan R Shuldiner15, Bradford Towne8, Henry Völzke13,37,38, Henri Wallaschofski24, James G Wilson39, Matthew Allison40, Cecilia M Lindgren41, Wolfram Goessling6,42,43,44,45, L Adrienne Cupples1,3, Matthew L Steinhauser5,6,45,46, Caroline S Fox1,47.
Abstract
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 of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.Entities:
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Year: 2016 PMID： 27918534 PMCID： PMC5451114 DOI： 10.1038/ng.3738
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330