Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation

Audrey Y. Chu, Xuan Deng, Virginia A. Fisher, Alexander Drong, Yang Zhang, Mary F. Feitosa, Ching Ti Liu, Olivia Weeks, Audrey C. Choh, Qing Duan, Thomas D. Dyer, John D. Eicher, Xiuqing Guo, Nancy L. Heard-Costa, Tim Kacprowski, Jack W. Kent, Leslie A. Lange, Xinggang Liu, Kurt Lohman, Lingyi LuAnubha Mahajan, Jeffrey R. O'Connell, Ankita Parihar, Juan M. Peralta, Albert V. Smith, Yi Zhang, Georg Homuth, Ahmed H. Kissebah, Joel Kullberg, René Laqua, Lenore J. Launer, Matthias Nauck, Michael Olivier, Patricia A. Peyser, James G. Terry, Mary K. Wojczynski, Jie Yao, Lawrence F. Bielak, John Blangero, Ingrid B. Borecki, Donald W. Bowden, John Jeffrey Carr, Stefan A. Czerwinski, Jingzhong Ding, Nele Friedrich, Vilmunder Gudnason, Tamara B. Harris, Erik Ingelsson, Andrew D. Johnson, Sharon L.R. Kardia, Carl D. Langefeld, Lars Lind, Yongmei Liu, Braxton D. Mitchell, Andrew P. Morris, Thomas H. Mosley, Jerome I. Rotter, Alan R. Shuldiner, Bradford Towne, Henry Völzke, Henri Wallaschofski, James G. Wilson, Matthew Allison, Cecilia M. Lindgren, Wolfram Goessling, L. Adrienne Cupples, Matthew L. Steinhauser, Caroline S. Fox

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)125-130
Number of pages6
JournalNature Genetics
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2017

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    Chu, A. Y., Deng, X., Fisher, V. A., Drong, A., Zhang, Y., Feitosa, M. F., Liu, C. T., Weeks, O., Choh, A. C., Duan, Q., Dyer, T. D., Eicher, J. D., Guo, X., Heard-Costa, N. L., Kacprowski, T., Kent, J. W., Lange, L. A., Liu, X., Lohman, K., ... Fox, C. S. (2017). Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation. Nature Genetics, 49(1), 125-130. https://doi.org/10.1038/ng.3738