A genome-wide association meta-analysis identifies new childhood obesity loci

被引：307

作者：

Bradfield, Jonathan P. ^{[1
]}

Taal, H. Rob ^{[2
,3
,4
]}

Timpson, Nicholas J. ^{[5
]}

Scherag, Andre ^{[6
]}

Lecoeur, Cecile ^{[7
]}

Warrington, Nicole M. ^{[8
]}

Hypponen, Elina ^{[9
]}

Holst, Claus ^{[10
]}

Valcarcel, Beatriz ^{[11
]}

Thiering, Elisabeth ^{[12
]}

Salem, Rany M. ^{[13
,14
,15
,16
,17
,18
]}

Schumacher, Fredrick R. ^{[19
]}

Cousminer, Diana L. ^{[20
]}

Sleiman, Patrick M. A. ^{[1
,21
,22
]}

Zhao, Jianhua ^{[21
]}

Berkowitz, Robert I. ^{[23
,24
]}

Vimaleswaran, Karani S. ^{[9
]}

Jarick, Ivonne ^{[25
]}

Pennell, Craig E. ^{[8
]}

Evans, David M. ^{[5
]}

St Pourcain, Beate ^{[5
]}

Berry, Diane J. ^{[9
]}

Mook-Kanamori, Dennis O. ^{[2
,3
,4
,26
]}

Hofman, Albert ^{[2
,3
]}

Rivadeneira, Fernando ^{[3
,27
]}

Uitterlinden, Andre G. ^{[3
,27
]}

van Duijn, Cornelia M. ^{[3
]}

van der Valk, Ralf J. P. ^{[2
,28
,29
]}

de Jongste, Johan C. ^{[2
,29
]}

Postma, Dirkje S. ^{[30
]}

Boomsma, Dorret I. ^{[31
]}

Gauderman, W. James ^{[19
]}

Hassanein, Mohamed T. ^{[19
]}

Lindgren, Cecilia M. ^{[32
]}

Magi, Reedik ^{[32
,33
]}

Boreham, Colin A. G. ^{[34
]}

Neville, Charlotte E. ^{[35
]}

Moreno, Luis A. ^{[36
,37
]}

Elliott, Paul ^{[11
]}

Pouta, Anneli ^{[38
]}

Hartikainen, Anna-Liisa ^{[39
]}

Li, Mingyao ^{[40
]}

Raitakari, Olli ^{[41
,42
]}

Lehtimaki, Terho ^{[43
,44
]}

Eriksson, Johan G. ^{[45
,46
,47
,48
]}

Palotie, Aarno ^{[18
,20
,49
,50
,51
]}

Dallongeville, Jean ^{[52
]}

Das, Shikta ^{[11
]}

Deloukas, Panos ^{[49
]}

McMahon, George ^{[53
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA

[2] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands

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

[4] Erasmus MC, Dept Pediat, Rotterdam, Netherlands

[5] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Sch Social & Community Med, Bristol, Avon, England

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

[7] Univ Lille Nord France, CNRS 8199, Inst Pasteur, Lille, France

[8] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia

[9] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, MRC Ctr Epidemiol Child Hlth, London, England

[10] Copenhagen Univ Hosp, Inst Prevent Med, Copenhagen, Denmark

[11] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC Hlth Protect Agcy HPA, Ctr Environm & Hlth,Sch Publ Hlth,Fac Med, London, England

[12] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol 1, Neuherberg, Germany

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

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

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

[16] Broad Inst, Metab Program, Cambridge, MA USA

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

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

[19] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[20] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[21] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[22] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[23] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA

[24] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA

[25] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany

[26] Weill Cornell Med Coll Qatar, Dept Physiol & Biophys, Doha, Qatar

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

[28] Univ Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp, Univ Med Ctr Groningen,GRIAC,Res Inst, Groningen, Netherlands

[29] Erasmus Univ, Div Resp Med, Dept Pediat, Med Ctr,Sophia Childrens Hosp, Rotterdam, Netherlands

[30] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Med & TB, GRIAC Res Inst, Groningen, Netherlands

[31] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

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

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

[34] Univ Coll Dublin, Inst Sport & Hlth, Dublin 2, Ireland

[35] Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci B, Belfast, Antrim, North Ireland

[36] Univ Zaragoza, Growth Exercise Nutr & Dev GENUD Res Grp, Zaragoza, Spain

[37] Univ Zaragoza, Sch Hlth Sci EUCS, Zaragoza, Spain

[38] Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland

[39] Univ Oulu, Inst Clin Med Obstet & Gynecol, Oulu, Finland

[40] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[41] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland

[42] Univ Turku, Turku, Finland

[43] Tampere Univ Hosp, Dept Clin Chem, Tampere, Finland

[44] Univ Tampere, FIN-33101 Tampere, Finland

[45] Natl Inst Hlth & Welf, Helsinki, Finland

[46] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland

[47] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland

[48] Folkhalsan Res Ctr, Helsinki, Finland

[49] Wellcome Trust Sanger Inst, Cambridge, England

[50] Univ Helsinki, Dept Med Genet, Helsinki, Finland

来源：

NATURE GENETICS | 2012年 / 44卷 / 05期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

BODY-MASS INDEX; HELICOBACTER-PYLORI; PREVENTION; OVERWEIGHT; BMI;

D O I：

10.1038/ng.2247

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (>= 95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 x 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous metaanalysis of adult BMI1.

引用

页码：526 / +

页数：7

共 16 条

[1] The Eradication of Helicobacter pylori is Affected by Body Mass Index (BMI) [J].

Abdullahi, Mohamed ;

Annibale, Bruno ;

Capoccia, Danila ;

Tari, Roberto ;

Lahner, Edith ;

Osborn, John ;

Leonetti, Frida ;

Severi, Carola .

OBESITY SURGERY, 2008, 18 (11) :1450-1454

[2] The prevalence of Helicobacter pylori in obese subjects [J].

Arslan, Erol ;

Atilgan, Halil ;

Yavasoglu, Irfan .

EUROPEAN JOURNAL OF INTERNAL MEDICINE, 2009, 20 (07) :695-697

[3] Overweight in children and adolescents - Pathophysiology, consequences, prevention, and treatment [J].

Daniels, SR ;

Arnett, DK ;

Eckel, RH ;

Gidding, SS ;

Hayman, LL ;

Kumanyika, S ;

Robinson, TN ;

Scott, BJ ;

St Jeor, S ;

Williams, CL .

CIRCULATION, 2005, 111 (15) :1999-2012

[4] Switch from Stress Response to Homeobox Transcription Factors in Adipose Tissue After Profound Fat Loss [J].

Dankel, Simon N. ;

Fadnes, Dag J. ;

Stavrum, Anne-Kristin ;

Stansberg, Christine ;

Holdhus, Rita ;

Hoang, Tuyen ;

Veum, Vivian L. ;

Christensen, Bjorn Jostein ;

Vage, Villy ;

Sagen, Jorn V. ;

Steen, Vidar M. ;

Mellgren, Gunnar .

PLOS ONE, 2010, 5 (06)

[5] Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence Influence of Loci Identified by Genome-Wide Association Studies [J].

den Hoed, Marcel ;

Ekelund, Ulf ;

Brage, Soren ;

Grontved, Anders ;

Zhao, Jing Hua ;

Sharp, Stephen J. ;

Ong, Ken K. ;

Wareham, Nicholas J. ;

Loos, Ruth J. F. .

DIABETES, 2010, 59 (11) :2980-2988

[6] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[7] Weight-for-stature compared with body mass index-for-age growth charts for the United States from the Centers for Disease Control and Prevention [J].

Flegal, KM ;

Wei, R ;

Ogden, C .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 2002, 75 (04) :761-766

[8] A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity [J].

Frayling, Timothy M. ;

Timpson, Nicholas J. ;

Weedon, Michael N. ;

Zeggini, Eleftheria ;

Freathy, Rachel M. ;

Lindgren, Cecilia M. ;

Perry, John R. B. ;

Elliott, Katherine S. ;

Lango, Hana ;

Rayner, Nigel W. ;

Shields, Beverley ;

Harries, Lorna W. ;

Barrett, Jeffrey C. ;

Ellard, Sian ;

Groves, Christopher J. ;

Knight, Bridget ;

Patch, Ann-Marie ;

Ness, Andrew R. ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Ring, Susan M. ;

Ben-Shlomo, Yoav ;

Jarvelin, Marjo-Riitta ;

Sovio, Ulla ;

Bennett, Amanda J. ;

Melzer, David ;

Ferrucci, Luigi ;

Loos, Ruth J. F. ;

Barroso, Ines ;

Wareham, Nicholas J. ;

Karpe, Fredrik ;

Owen, Katharine R. ;

Cardon, Lon R. ;

Walker, Mark ;

Hitman, Graham A. ;

Palmer, Colin N. A. ;

Doney, Alex S. F. ;

Morris, Andrew D. ;

Smith, George Davey ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

SCIENCE, 2007, 316 (5826) :889-894

[9] HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts [J].

Fu, M ;

Lui, VCH ;

Sham, MH ;

Cheung, ANY ;

Tam, PKH .

DEVELOPMENTAL DYNAMICS, 2003, 228 (01) :1-10

[10] Sleeve Gastrectomy Leads to Helicobacter pylori Eradication [J].

Keren, Dean ;

Matter, Ibrahim ;

Rainis, Tova ;

Goldstein, Omer ;

Stermer, Edy ;

Lavy, Alexandra .

OBESITY SURGERY, 2009, 19 (06) :751-756

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