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

被引：100

作者：

Chu, Audrey Y. ^{[1
,2
,3
,52
]}

Deng, Xuan ^{[4
]}

Fisher, Virginia A. ^{[4
]}

Drong, Alexander ^{[5
]}

Zhang, Yang ^{[3
,6
,7
]}

Feitosa, Mary F. ^{[8
]}

Liu, Ching-Ti ^{[4
]}

Weeks, Olivia ^{[3
,7
]}

Choh, Audrey C. ^{[9
]}

Duan, Qing ^{[10
]}

Dyer, Thomas D. ^{[11
,12
]}

Eicher, John D. ^{[1
]}

Guo, Xiuqing ^{[13
]}

Heard-Costa, Nancy L. ^{[4
]}

Kacprowski, Tim ^{[14
,15
]}

Kent, Jack W., Jr. ^{[16
]}

Lange, Leslie A. ^{[10
]}

Liu, Xinggang ^{[17
]}

Lohman, Kurt ^{[18
,19
]}

Lu, Lingyi ^{[19
]}

Mahajan, Anubha ^{[5
]}

O'Connell, Jeffrey R. ^{[17
]}

Parihar, Ankita ^{[17
]}

Peralta, Juan M. ^{[11
,12
]}

Smith, Albert V. ^{[20
,21
]}

Zhang, Yi ^{[22
]}

Homuth, Georg ^{[14
]}

Kissebah, Ahmed H. ^{[22
]}

Kullberg, Joel ^{[23
]}

Laqua, Rene ^{[24
]}

Launer, Lenore J. ^{[25
]}

Nauck, Matthias ^{[15
,26
]}

Olivier, Michael ^{[16
,22
]}

Peyser, Patricia A. ^{[27
]}

Terry, James G. ^{[28
,29
]}

Wojczynski, Mary K. ^{[8
]}

Yao, Jie ^{[13
]}

Bielak, Lawrence F. ^{[27
]}

Blangero, John ^{[11
,12
]}

Borecki, Ingrid B. ^{[8
]}

Bowden, Donald W. ^{[30
,31
,32
]}

Carr, John Jeffrey ^{[28
,29
]}

Czerwinski, Stefan A. ^{[33
]}

Ding, Jingzhong ^{[18
,34
]}

Friedrich, Nele ^{[15
,26
]}

Gudnason, Vilmunder ^{[20
,21
]}

Harris, Tamara B. ^{[25
]}

Ingelsson, Erik ^{[35
,36
]}

Johnson, Andrew D. ^{[1
]}

Kardia, Sharon L. R. ^{[27
]}

机构：

[1] NHLBIs Framingham Heart Study, Framingham, MA USA

[2] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[5] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[6] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA

[8] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[9] Wright State Univ, Boonshoft Sch Med, Dept Populat & Publ Hlth Sci, Div Epidemiol & Biostat, Dayton, OH 45435 USA

[10] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[11] Univ Texas Hlth Sci Ctr San Antonio, South Texas Diabet & Obes Inst, Brownsville, TX USA

[12] Univ Texas Rio Grande Valley, Brownsville, TX USA

[13] UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, LABioMed Harbor, Torrance, CA USA

[14] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[15] German Ctr Cardiovasc Res DZHK, Greifswald, Germany

[16] Texas Biomed Res Inst, Dept Genet, TOPS Nutr & Obes Res Ctr, San Antonio, TX USA

[17] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[18] Wake Forest Sch Med, Winston Salem, NC USA

[19] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA

[20] Iceland Heart Assoc, Kopavogur, Iceland

[21] Univ Iceland, Fac Med, Reykjavik, Iceland

[22] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, TOPS Obes & Metab Res Ctr, Dept Psychol, Milwaukee, WI 53226 USA

[23] Uppsala Univ, Sect Radiol, Dept Surg Sci, Uppsala, Sweden

[24] Univ Hosp Berne, Dept Neuroradiol, Bern, Switzerland

[25] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA

[26] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany

[27] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

[28] Vanderbilt Univ, Med Ctr, Dept Cardiovasc Med, Dept Radiol & Radiol Sci, Nashville, TN USA

[29] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA

[30] Wake Forest Univ Hlth Sci, Ctr Genom & Personalized Med Res, Winston Salem, NC USA

[31] Wake Forest Univ, Sch Med, Ctr Diabet Res, Dept Biochem, Winston Salem, NC 27109 USA

[32] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA

[33] Univ Texas Hlth Sci Ctr UTHealth, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Brownsville Campus, Brownsville, TX USA

[34] Wake Forest Sch Med, Gerontol & Geriatr Med, Winston Salem, NC USA

[35] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden

[36] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA

[37] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA

[38] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA

[39] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England

[40] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA

[41] Univ Med Greifswald, Inst Community Med, Greifswald, Germany

[42] German Ctr Diabet Res DZD, Greifswald, Germany

[43] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA

[44] Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA

[45] Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England

[46] Harvard Stem Cell Inst, Cambridge, MA USA

[47] Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA USA

[48] Dana Farber Canc Inst, Boston, MA 02115 USA

[49] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[50] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

INCIDENT CARDIOVASCULAR-DISEASE; METABOLIC RISK-FACTORS; ALL-CAUSE MORTALITY; CARDIOMETABOLIC RISK; VISCERAL ADIPOSITY; SUBCUTANEOUS FAT; SUSCEPTIBILITY; HYPERTENSION; QUALITY; BIOLOGY;

D O I：

10.1038/ng.3738

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 ectopicfat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 x 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.

引用

页码：125 / 130

页数：6

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