Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

被引：2188

作者：

Speliotes, Elizabeth K. ^{[2
,3
]}

Willer, Cristen J. ^{[4
]}

Berndt, Sonja I. ^{[5
]}

Monda, Keri L. ^{[6
]}

Thorleifsson, Gudmar ^{[7
]}

Jackson, Anne U. ^{[4
]}

Allen, Hana Lango ^{[8
]}

Lindgren, Cecilia M. ^{[9
,10
]}

Luan, Jian'an ^{[11
]}

Maegi, Reedik ^{[9
]}

Randall, Joshua C. ^{[9
]}

Vedantam, Sailaja ^{[2
,12
,13
,14
]}

Winkler, Thomas W. ^{[15
]}

Qi, Lu ^{[16
,17
,18
]}

Workalemahu, Tsegaselassie ^{[16
]}

Heid, Iris M. ^{[15
,19
]}

Steinthorsdottir, Valgerdur ^{[7
]}

Stringham, Heather M. ^{[4
]}

Weedon, Michael N. ^{[8
]}

Wheeler, Eleanor ^{[20
]}

Wood, Andrew R. ^{[8
]}

Ferreira, Teresa ^{[9
]}

Weyant, Robert J. ^{[4
]}

Segre, Ayellet V. ^{[21
,22
,24
]}

Estrada, Karol ^{[25
,26
,27
]}

Liang, Liming ^{[28
,29
]}

Nemesh, James ^{[22
,23
]}

Park, Ju-Hyun ^{[5
]}

Gustafsson, Stefan ^{[30
]}

Kilpelaenen, Tuomas O. ^{[11
]}

Yang, Jian ^{[31
]}

Bouatia-Naji, Nabila ^{[32
,33
]}

Esko, Tonu ^{[34
,36
]}

Feitosa, Mary F. ^{[37
]}

Kutalik, Zoltan ^{[38
,39
]}

Mangino, Massimo ^{[40
]}

Raychaudhuri, Soumya ^{[22
,23
,41
]}

Scherag, Andre ^{[42
]}

Smith, Albert Vernon ^{[43
,44
]}

Welch, Ryan ^{[4
]}

Zhao, Jing Hua ^{[11
]}

Aben, Katja K. ^{[45
]}

Absher, Devin M. ^{[46
]}

Amin, Najaf ^{[25
]}

Dixon, Anna L. ^{[47
]}

Fisher, Eva ^{[48
]}

Glazer, Nicole L. ^{[49
,50
]}

Goddard, Michael E. ^{[51
,52
]}

Heard-Costa, Nancy L. ^{[53
]}

Hoesel, Volker ^{[54
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge, England

[2] Broad Inst, Metab Initiat & Program Med & Populat Genet, Cambridge, MA USA

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

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

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

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

[7] deCODE Genet, Reykjavik, Iceland

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

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

[10] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

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

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

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

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

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

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

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

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

[19] Helmholtz Zentrum Munchen, German Res Ctr, Inst Epidemiol, Neuherberg, Germany

[20] Wellcome Trust Sanger Inst, Cambridge, England

[21] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

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

[23] MIT, Cambridge, MA 02139 USA

[24] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[25] Erasmus Med Ctr MC, Dept Epidemiol, Rotterdam, Netherlands

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

[27] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI Sponsored, Rotterdam, Netherlands

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

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

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

[31] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia

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

[33] Univ Lille Nord France, Lille, France

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

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

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

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

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

[39] Swiss Inst Bioinformat, Lausanne, Switzerland

[40] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[41] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA USA

[42] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany

[43] Iceland Heart Assoc, Kopavogur, Iceland

[44] Univ Iceland, Reykjavik, Iceland

[45] Comprehens Canc Ctr E, Nijmegen, Netherlands

[46] Hudson Alpha Inst Biotechnol, Huntsville, AL USA

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

[48] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany

[49] Univ Washington, Dept Med, Seattle, WA USA

[50] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 11期

基金：

英国医学研究理事会; 芬兰科学院; 澳大利亚研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GASTRIC-INHIBITORY POLYPEPTIDE; COMMON VARIANTS; EARLY-ONSET; FTO GENE; FAT MASS; OBESITY; GLUCOSE; METAANALYSIS; WEIGHT;

D O I：

10.1038/ng.686

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

引用

页码：937 / U53

页数：14

共 54 条

[1] Handling marker-marker linkage disequilibrium: Pedigree analysis with clustered markers [J].

Abecasis, GR ;

Wigginton, JE .

AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 77 (05) :754-767

[2]

Anderson JW, 2001, AM J CLIN NUTR, V74, P579

[3]

[Anonymous], 1998, OBES RES

[4] GenABEL: an R library for genome-wide association analysis [J].

Aulchenko, Yurii S. ;

Ripke, Stephan ;

Isaacs, Aaron ;

Van Duijn, Cornelia M. .

BIOINFORMATICS, 2007, 23 (10) :1294-1296

[5] ProbABEL package for genome-wide association analysis of imputed data [J].

Aulchenko, Yurii S. ;

Struchalin, Maksim V. ;

van Duijn, Cornelia M. .

BMC BIOINFORMATICS, 2010, 11

[6] Large, rare chromosomal deletions associated with severe early-onset obesity [J].

Bochukova, Elena G. ;

Huang, Ni ;

Keogh, Julia ;

Henning, Elana ;

Purmann, Carolin ;

Blaszczyk, Kasia ;

Saeed, Sadia ;

Hamilton-Shield, Julian ;

Clayton-Smith, Jill ;

O'Rahilly, Stephen ;

Hurles, Matthew E. ;

Farooqi, I. Sadaf .

NATURE, 2010, 463 (7281) :666-670

[7] Pro-opiomelanocortin (POMC)-derived peptides and the regulation of energy homeostasis [J].

Coll, Anthony P. ;

Tung, Y. C. Loraine .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2009, 300 (1-2) :147-151

[8] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[9] New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk [J].

Dupuis, Josee ;

Langenberg, Claudia ;

Prokopenko, Inga ;

Saxena, Richa ;

Soranzo, Nicole ;

Jackson, Anne U. ;

Wheeler, Eleanor ;

Glazer, Nicole L. ;

Bouatia-Naji, Nabila ;

Gloyn, Anna L. ;

Lindgren, Cecilia M. ;

Magi, Reedik ;

Morris, Andrew P. ;

Randall, Joshua ;

Johnson, Toby ;

Elliott, Paul ;

Rybin, Denis ;

Thorleifsson, Gudmar ;

Steinthorsdottir, Valgerdur ;

Henneman, Peter ;

Grallert, Harald ;

Dehghan, Abbas ;

Hottenga, Jouke Jan ;

Franklin, Christopher S. ;

Navarro, Pau ;

Song, Kijoung ;

Goel, Anuj ;

Perry, John R. B. ;

Egan, Josephine M. ;

Lajunen, Taina ;

Grarup, Niels ;

Sparso, Thomas ;

Doney, Alex ;

Voight, Benjamin F. ;

Stringham, Heather M. ;

Li, Man ;

Kanoni, Stavroula ;

Shrader, Peter ;

Cavalcanti-Proenca, Christine ;

Kumari, Meena ;

Qi, Lu ;

Timpson, Nicholas J. ;

Gieger, Christian ;

Zabena, Carina ;

Rocheleau, Ghislain ;

Ingelsson, Erik ;

An, Ping ;

O'Connell, Jeffrey ;

Luan, Jian'an ;

Elliott, Amanda .

NATURE GENETICS, 2010, 42 (02) :105-U32

[10] Genetics of gene expression and its effect on disease [J].

Emilsson, Valur ;

Thorleifsson, Gudmar ;

Zhang, Bin ;

Leonardson, Amy S. ;

Zink, Florian ;

Zhu, Jun ;

Carlson, Sonia ;

Helgason, Agnar ;

Walters, G. Bragi ;

Gunnarsdottir, Steinunn ;

Mouy, Magali ;

Steinthorsdottir, Valgerdur ;

Eiriksdottir, Gudrun H. ;

Bjornsdottir, Gyda ;

Reynisdottir, Inga ;

Gudbjartsson, Daniel ;

Helgadottir, Anna ;

Jonasdottir, Aslaug ;

Jonasdottir, Adalbjorg ;

Styrkarsdottir, Unnur ;

Gretarsdottir, Solveig ;

Magnusson, Kristinn P. ;

Stefansson, Hreinn ;

Fossdal, Ragnheidur ;

Kristjansson, Kristleifur ;

Gislason, Hjortur G. ;

Stefansson, Tryggvi ;

Leifsson, Bjorn G. ;

Thorsteinsdottir, Unnur ;

Lamb, John R. ;

Gulcher, Jeffrey R. ;

Reitman, Marc L. ;

Kong, Augustine ;

Schadt, Eric E. ;

Stefansson, Kari .

NATURE, 2008, 452 (7186) :423-U2

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