Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

被引：1032

作者：

Anderson, Carl A. ^{[1
]}

Boucher, Gabrielle ^{[2
,3
]}

Lees, Charlie W. ^{[4
]}

Franke, Andre ^{[5
]}

D'Amato, Mauro ^{[6
]}

Taylor, Kent D. ^{[7
]}

Lee, James C. ^{[8
]}

Goyette, Philippe ^{[2
,3
]}

Imielinski, Marcin ^{[9
]}

Latiano, Anna ^{[10
]}

Lagace, Caroline ^{[2
,3
]}

Scott, Regan ^{[11
]}

Amininejad, Leila ^{[12
]}

Bumpstead, Suzannah ^{[1
]}

Baidoo, Leonard ^{[11
]}

Baldassano, Robert N. ^{[13
]}

Barclay, Murray ^{[14
]}

Bayless, Theodore M. ^{[15
]}

Brand, Stephan ^{[16
]}

Buening, Carsten ^{[17
]}

Colombel, Jean-Frederic ^{[18
]}

Denson, Lee A. ^{[19
]}

De Vos, Martine ^{[20
]}

Dubinsky, Marla ^{[21
]}

Edwards, Cathryn ^{[22
]}

Ellinghaus, David ^{[5
]}

Fehrmann, Rudolf S. N. ^{[23
]}

Floyd, James A. B. ^{[1
]}

Florin, Timothy ^{[24
]}

Franchimont, Denis ^{[12
]}

Franke, Lude ^{[23
]}

Georges, Michel ^{[25
]}

Glas, Juergen ^{[16
]}

Glazer, Nicole L. ^{[26
]}

Guthery, Stephen L. ^{[27
]}

Haritunians, Talin ^{[28
]}

Hayward, Nicholas K. ^{[29
]}

Hugot, Jean-Pierre

Jobin, Gilles ^{[2
,31
]}

Laukens, Debby ^{[20
]}

Lawrance, Ian ^{[32
]}

Lemann, Marc ^{[30
]}

Levine, Arie ^{[33
,34
]}

Libioulle, Cecile ^{[35
]}

Louis, Edouard ^{[35
]}

McGovern, Dermot P. ^{[7
,28
]}

Milla, Monica ^{[36
]}

Montgomery, Grant W. ^{[37
]}

Morley, Katherine I. ^{[1
]}

Mowat, Craig ^{[38
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge, England

[2] Univ Montreal, Montreal, PQ, Canada

[3] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada

[4] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr, Edinburgh, Midlothian, Scotland

[5] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[6] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden

[7] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA

[8] Univ Cambridge, Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge CB2 2QQ, England

[9] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[10] IRCCS CSS Hosp, Gastroenterol Unit, San Giovanni Rotondo, Italy

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

[12] Free Univ Brussels, Erasmus Hosp, Dept Gastroenterol, Brussels, Belgium

[13] Childrens Hosp Philadelphia, Dept Pediat, Ctr Pediat Inflammatory Bowel Dis, Philadelphia, PA 19104 USA

[14] Univ Otago, Dept Med, Christchurch, New Zealand

[15] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA

[16] Univ Hosp Munich, Dept Med 2, Munich, Germany

[17] Univ Med Berlin, Dept Gastroenterol, Charite, Berlin, Germany

[18] Univ Lille, Dept Hepatogastroenterol, Lille, France

[19] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA

[20] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium

[21] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA

[22] Torbay Hosp, Dept Gastroenterol, Torquay, Devon, England

[23] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[24] Dept Gastroenterol, Mater Hlth Serv, Brisbane, Qld, Australia

[25] Univ Liege, Dept Genet, Fac Vet Med, Liege, Belgium

[26] Univ Washington, Cardiovasc Hlth Res Unit, Dept Internal Med, Seattle, WA 98195 USA

[27] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA

[28] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[29] Queensland Inst Med Res, Oncogenom Lab, Brisbane, Qld 4006, Australia

[30] Univ Paris Diderot, GETAID Grp, Paris, France

[31] Hop Maison Neuve Rosemont, Dept Gastroenterol, Montreal, PQ H1T 2M4, Canada

[32] Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA, Australia

[33] Tel Aviv Univ, Pediat Gastroenterol Unit, Wolfson Med Ctr, IL-69978 Tel Aviv, Israel

[34] Sackler Sch Med, Tel Aviv, Israel

[35] Ctr Hosp Univ Univ Liege, Div Gastroenterol, Liege, Belgium

[36] Azienda Ospeda Univ AOU Careggi, Unit Gastroenterol SOD2, Florence, Italy

[37] Queensland Inst Med Res, Mol Epidemiol, Brisbane, Qld 4006, Australia

[38] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland

[39] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA

[40] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[41] Univ Manchester, Dept Med Genet, Manchester, Lancs, England

[42] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[43] Univ Florence, Inst Human Genet, Florence, Italy

[44] Univ Hosp Nancy, Dept Hepatogastroenterol, Vandoeuvre Les Nancy, France

[45] Hosp Clin Barcelona, Dept Gastroenterol, IDIBAPS, CIBERehd, Barcelona, Spain

[46] Kings Coll London, Sch Med, Dept Med & Mol Genet, Guys Hosp, London WC2R 2LS, England

[47] Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA

[48] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland

[49] Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium

[50] St Thomas Hosp, Dept Gastroenterol, Guys & St Thomas NHS Fdn Trust, London, England

来源：

NATURE GENETICS | 2011年 / 43卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CROHNS-DISEASE; COMMON VARIANTS; MULTIPLE; PROTEIN; EXPRESSION; ENRICHMENT; RECEPTOR; BLIMP-1;

D O I：

10.1038/ng.764

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

引用

页码：246 / U94

页数：9

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[41] Gα12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly [J].