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
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
收藏
页码:246 / U94
页数:9
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