Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

被引：390

作者：

Lindgren, Cecilia M. ^{[1
]}

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

Randall, Joshua C. ^{[1
]}

Lamina, Claudia ^{[2
,4
]}

Steinthorsdottir, Valgerdur ^{[5
]}

Qi, Lu ^{[6
,7
]}

Speliotes, Elizabeth K. ^{[8
,9
]}

Thorleifsson, Gudmar ^{[5
]}

Willer, Cristen J. ^{[10
]}

Herrera, Blanca M. ^{[1
,11
]}

Jackson, Anne U. ^{[10
]}

Lim, Noha ^{[12
]}

Scheet, Paul ^{[10
,12
]}

Soranzo, Nicole ^{[13
,14
]}

Amin, Najaf ^{[15
]}

Aulchenko, Yurii S. ^{[15
]}

Chambers, John C. ^{[16
]}

Drong, Alexander ^{[1
]}

Luan, Jian'an ^{[17
]}

Lyon, Helen N. ^{[9
,18
]}

Rivadeneira, Fernando ^{[15
,19
]}

Sanna, Serena ^{[20
]}

Timpson, Nicholas J. ^{[21
]}

Zillikens, M. Carola ^{[19
]}

Zhao, Jing Hua ^{[17
]}

Almgren, Peter ^{[22
]}

Bandinelli, Stefania ^{[23
]}

Bennett, Amanda J. ^{[11
]}

Bergman, Richard N. ^{[24
]}

Bonnycastle, Lori L. ^{[25
]}

Bumpstead, Suzannah J. ^{[14
]}

Chanock, Stephen J. ^{[26
]}

Cherkas, Lynn ^{[13
]}

Chines, Peter ^{[25
]}

Coin, Lachlan ^{[27
]}

Cooper, Cyrus ^{[28
]}

Crawford, Gabriel ^{[29
]}

Doering, Angela ^{[2
]}

Dominiczak, Anna ^{[30
]}

Doney, Alex S. F. ^{[31
]}

Ebrahim, Shah ^{[32
]}

Elliott, Paul ^{[27
]}

Erdos, Michael R. ^{[25
]}

Estrada, Karol ^{[19
]}

Ferrucci, Luigi ^{[33
]}

Fischer, Guido ^{[2
]}

Forouhi, Nita G.

Gieger, Christian ^{[2
]}

Grallert, Harald ^{[2
]}

Groves, Christopher J. ^{[11
]}

机构：

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

[2] Natl Res Ctr Environm & Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[3] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany

[4] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria

[5] deCODE Genet, Reykjavik, Iceland

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

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

[8] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol, Boston, MA USA

[9] Broad Inst MIT & Harvard, Metab Initiat & Program Med & Populat Genet, Boston, MA USA

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

[11] Univ Oxford, Dept Endocrinol & Metab, Oxford Ctr Diabet, Oxford, England

[12] Clin Pharmacol & Discovery Med, Med Genet, King Of Prussia, PA USA

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

[14] Wellcome Trust Sanger Inst, Cambridge, England

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

[16] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England

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

[18] Childrens Hosp, Div Genet & Endocrinol, Program Genom, Boston, MA 02115 USA

[19] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[20] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy

[21] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[22] Lund Univ, Malmo Univ Hosp, Diabet & Endocrinol Res Unit, Dept Clin Sci, Malmo, Sweden

[23] ASF, Geriatr Unit, Florence, Italy

[24] Univ So Calif, Sch Med, Los Angeles, CA USA

[25] NHGRI, Bethesda, MD 20892 USA

[26] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[27] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England

[28] Univ Southampton, MRC, Epidemiol Resource Ctr, Southampton, Hants, England

[29] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[30] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland

[31] Univ Dundee, Ninewells Hosp & Med Sch, Div Med & Therapeut, Diabet Res Grp, Dundee DD1 9SY, Scotland

[32] Univ Bristol, Dept Social Med, Bristol, Avon, England

[33] NIA, Clin Res Branch, Baltimore, MD 21224 USA

[34] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA

[35] St Georges Univ London, Div Community Hlth Sci, London, England

[36] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden

[37] KTL Natl Publ Hlth Inst, Helsinki, Finland

[38] Univ Southampton, Div Human Genet, Southampton, Hants, England

[39] Malmska Municipal Hlth Ctr & Hosp, Folkhalsan Res Ctr, Pietarsaari, Finland

[40] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland

[41] Finnish Inst Occpat Hlth, Oulu, Finland

[42] Ctr Natl Genotypage, Evry, France

[43] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England

[44] Umea Univ, Dept Surg & Perioperat Sci, Sect Sports Med, Umea, Sweden

[45] Umea Univ Hosp, Dept Community Med & Rehabil, Sect Geriatr, S-90185 Umea, Sweden

[46] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[47] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland

[48] Univ Oxford, Dept Cardiovasc Med, Oxford, England

[49] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden

[50] Univ Oulu, Dept Clin Chem, Oulu, Finland

来源：

PLOS GENETICS | 2009年 / 5卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会; 芬兰科学院; 美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

FTO GENE; WAIST CIRCUMFERENCE; ADULT OBESITY; ENVIRONMENTAL-CONDITIONS; INSULIN-RESISTANCE; SEQUENCE VARIANTS; COMMON VARIANTS; EXPRESSION; IMPUTATION; HEIGHT;

D O I：

10.1371/journal.pgen.1000508

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

引用

页数：13

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