Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.
Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.
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DOI：
10.1038/ng.3738
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发表时间：
2017-01
期刊：
影响因子：
30.8
通讯作者：
Fox CS
中科院分区：
文献类型：
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作者：
Chu AY;Deng X;Fisher VA;Drong A;Zhang Y;Feitosa MF;Liu CT;Weeks O;Choh AC;Duan Q;Dyer TD;Eicher JD;Guo X;Heard-Costa NL;Kacprowski T;Kent JW Jr;Lange LA;Liu X;Lohman K;Lu L;Mahajan A;O'Connell JR;Parihar A;Peralta JM;Smith AV;Zhang Y;Homuth G;Kissebah AH;Kullberg J;Laqua R;Launer LJ;Nauck M;Olivier M;Peyser PA;Terry JG;Wojczynski MK;Yao J;Bielak LF;Blangero J;Borecki IB;Bowden DW;Carr JJ;Czerwinski SA;Ding J;Friedrich N;Gudnason V;Harris TB;Ingelsson E;Johnson AD;Kardia SL;Langefeld CD;Lind L;Liu Y;Mitchell BD;Morris AP;Mosley TH Jr;Rotter JI;Shuldiner AR;Towne B;Völzke H;Wallaschofski H;Wilson JG;Allison M;Lindgren CM;Goessling W;Cupples LA;Steinhauser ML;Fox CS
体脂肪分布的变化有助于肥胖的代谢后遗症。体脂分布的遗传决定因素知之甚少。本研究的目的是通过对欧洲、非洲、西班牙裔和中国血统人群中多达9，594名女性和8，738名男性的6种异位脂肪性状进行样本量加权固定效应全基因组关联荟萃分析，获得对体脂分布的潜在遗传学的新见解，有和没有性别分层。总共发现了7个与异位脂肪性状相关的新基因座（ATXN 1、UBE 2 E2、EBF 1、RREB 1、GSDMB、GRAMD 3和ENSA; P<5×10−8; FDR<1%）。对这些基因的功能分析显示，ATXN 1和UBE 2 E2在原代小鼠脂肪祖细胞中的功能丧失损害了脂肪细胞分化，表明ATXN 1和UBE 2 E2在脂肪形成中的生理作用。未来的研究是必要的，以进一步探索这些基因影响脂肪细胞生物学的机制，以及它们的扰动如何导致全身性代谢疾病。
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.