Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

被引：2062

作者：

Barrett, Jeffrey C. ^{[2
]}

Hansoul, Sarah ^{[3
]}

Nicolae, Dan L. ^{[4
]}

Cho, Judy H. ^{[5
]}

Duerr, Richard H. ^{[6
,7
]}

Rioux, John D. ^{[1
,8
]}

Brant, Steven R. ^{[9
,10
]}

Silverberg, Mark S. ^{[11
]}

Taylor, Kent D. ^{[12
]}

Barmada, M. Michael

Bitton, Alain ^{[13
]}

Dassopoulos, Themistocles ^{[9
]}

Datta, Lisa Wu

Green, Todd ^{[1
]}

Griffiths, Anne M. ^{[14
]}

Kistner, Emily O. ^{[15
]}

Murtha, Michael T. ^{[5
]}

Regueiro, Miguel D.

Rotter, Jerome I. ^{[12
]}

Schumm, L. Philip

Steinhart, A. Hillary ^{[11
]}

Targan, Stephan R. ^{[12
]}

Xavier, Ramnik J. ^{[16
]}

Libioulle, Cecile ^{[3
]}

Sandor, Cynthia ^{[3
]}

Lathrop, Mark ^{[17
]}

Belaiche, Jacques

Dewit, Olivier ^{[18
]}

Gut, Ivo ^{[17
]}

Heath, Simon ^{[17
]}

Laukens, Debby ^{[19
]}

Mni, Myriam

Rutgeerts, Paul ^{[20
]}

Van Gossum, Andre ^{[21
]}

Zelenika, Diana ^{[17
]}

Franchimont, Denis ^{[21
]}

Hugot, Jean-Pierre ^{[22
]}

de Vos, Martine ^{[19
]}

Vermeire, Severine ^{[20
]}

Louis, Edouard

Cardon, Lon R. ^{[2
]}

Anderson, Carl A. ^{[2
]}

Drummond, Hazel ^{[23
]}

Nimmo, Elaine ^{[23
]}

Ahmad, Tariq ^{[24
]}

Prescott, Natalie J. ^{[25
]}

Onnie, Clive M. ^{[25
]}

Fisher, Sheila A. ^{[25
]}

Marchini, Jonathan ^{[26
]}

Ghori, Jilur

机构：

[1] MIT, Broad Inst, Cambridge, MA 02142 USA

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Bioinformat & Stat Genet, Oxford OX3 7BN, England

[3] Univ Liege, Unit Anim Genom, GIGA R, B-4000 Liege, Belgium

[4] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[5] Yale Univ, Dept Med, Div Gastroenterol, Inflammatory Bowel Dis Ctr, New Haven, CT 06519 USA

[6] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr,Univ Pittsburgh, Pittsburgh, PA 15213 USA

[7] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA

[8] Univ Montreal, Montreal, PQ H1T 1C8, Canada

[9] Johns Hopkins Univ, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21231 USA

[10] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

[11] Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada

[12] Cedars Sinai Med Ctr, Med Genet Inst Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

[13] McGill Univ, Royal Victoria Hosp, Dept Med, Montreal, PQ H3A 1A1, Canada

[14] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[15] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

[16] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[17] Ctr Natl Genotypage, Evry, France

[18] Clin Univ St Luc, Dept Gastroenterol, UCL, B-1200 Brussels, Belgium

[19] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, Ghent, Belgium

[20] Katholieke Univ Leuven Hosp, Dept Gastroenterol, Louvain, Belgium

[21] Free Univ Brussels, Erasmus Hosp, Dept Gastroenterol, B-1050 Brussels, Belgium

[22] INSERM, F-75654 Paris 13, France

[23] Univ Edinburgh, Western Gen Hosp, Sch Mol & Clin Med, Div Med Sci,Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[24] Peninsula Med Sch, Exeter EX2 5DW, Devon, England

[25] Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England

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

[27] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[28] Univ Cambridge, Addenbrookes Hosp, IBD Res Grp, Cambridge CB2 2QQ, England

[29] Univ Newcastle Upon Tyne, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[30] Univ Oxford, Dept Infirm, Gastroenterol Unit, Oxford OX2 6HE, England

[31] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 08期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/ng.175

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease ( a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.

引用

页码：955 / 962

页数：8

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