Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

被引：708

作者：

Heid, Iris M. ^{[2
,3
]}

Jackson, Anne U. ^{[4
]}

Randall, Joshua C. ^{[1
]}

Winkler, Thomas W. ^{[2
]}

Qi, Lu ^{[5
,6
,7
]}

Steinthorsdottir, Valgerdur ^{[8
]}

Thorleifsson, Gudmar ^{[8
]}

Zillikens, M. Carola ^{[9
,10
]}

Speliotes, Elizabeth K. ^{[11
,12
,13
]}

Maegi, Reedik ^{[1
]}

Workalemahu, Tsegaselassie ^{[5
]}

White, Charles C. ^{[14
]}

Bouatia-Naji, Nabila ^{[15
,16
]}

Harris, Tamara B. ^{[17
]}

Berndt, Sonja I. ^{[18
]}

Ingelsson, Erik ^{[19
]}

Willer, Cristen J. ^{[4
]}

Weedon, Michael N. ^{[20
]}

Luan, Jianan ^{[21
]}

Vedantam, Sailaja ^{[11
,12
,22
,23
,24
]}

Esko, Tonu ^{[25
,26
,27
]}

Kilpelaeinen, Tuomas O. ^{[21
]}

Kutalik, Zoltan ^{[28
,29
]}

Li, Shengxu ^{[21
]}

Monda, Keri L. ^{[30
]}

Dixon, Anna L. ^{[31
]}

Holmes, Christopher C. ^{[32
,33
]}

Kaplan, Lee M. ^{[6
,13
,34
]}

Liang, Liming ^{[35
,36
]}

Min, Josine L. ^{[37
]}

Moffatt, Miriam F. ^{[38
]}

Molony, Cliona ^{[39
]}

Nicholson, George ^{[33
]}

Schadt, Eric E. ^{[40
,41
]}

Zondervan, Krina T. ^{[42
]}

Feitosa, Mary F. ^{[43
]}

Ferreira, Teresa ^{[1
]}

Allen, Hana Lango ^{[20
]}

Weyant, Robert J. ^{[4
]}

Wheeler, Eleanor ^{[44
]}

Wood, Andrew R. ^{[20
]}

Estrada, Karol ^{[9
,10
,45
]}

Goddard, Michael E. ^{[46
,47
]}

Lettre, Guillaume ^{[48
,49
]}

Mangino, Massimo ^{[50
]}

Nyholt, Dale R. ^{[51
]}

Purcell, Shaun ^{[52
,53
,54
]}

Smith, Albert Vernon ^{[55
,56
]}

Visscher, Peter M. ^{[57
]}

Yang, Jian ^{[57
]}

机构：

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

[2] Regensburg Univ Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[4] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[8] deCODE Genet, Reykjavik, Iceland

[9] Erasmus Med Ctr MC, Dept Internal Med, Rotterdam, Netherlands

[10] NGI, NCHA, Rotterdam, Netherlands

[11] Broad Inst, Metab Initiat, Cambridge, MA USA

[12] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[13] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

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

[15] Inst Pasteur, IBL, UMR8199, CNRS, F-59019 Lille, France

[16] Univ Lille Nord France, Lille, France

[17] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA

[18] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[19] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[20] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England

[21] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England

[22] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[23] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[24] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[25] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[26] Estonian Bioctr, Tartu, Estonia

[27] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia

[28] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[29] Swiss Inst Bioinformat, Lausanne, Switzerland

[30] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[31] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

[32] MRC Harwell, Oxford, England

[33] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[34] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA

[35] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[36] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[37] Leiden Univ, Med Ctr, Leiden, Netherlands

[38] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

[39] Merck & Co Inc, Merck Res Labs, Boston, MA USA

[40] Pacific Biosci, Menlo Pk, CA USA

[41] Sage Bionetworks, Seattle, WA USA

[42] Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England

[43] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[44] Wellcome Trust Sanger Inst, Cambridge, England

[45] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[46] Univ Melbourne, Parkville, Vic 3052, Australia

[47] Dept Primary Ind, Melbourne, Vic, Australia

[48] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada

[49] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

[50] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

瑞士国家科学基金会; 芬兰科学院; 英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; BODY-FAT; GLUCOSE-HOMEOSTASIS; ABDOMINAL ADIPOSITY; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON VARIANTS; RISK; OBESITY;

D O I：

10.1038/ng.685

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

引用

页码：949 / U160

页数：14

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