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

被引:297
|
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
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
收藏
页码:526 / +
页数:7
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