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

被引：1046

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：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

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

共 53 条

[1] Review Article: The genetics of inflammatory bowel disease [J].

Ahmad, T ;

Satsangi, J ;

Mcgovern, D ;

Bunce, M ;

Jewell, DP .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2001, 15 (06) :731-748

[2] A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population [J].

Asano, Kouichi ;

Matsushita, Tomonaga ;

Umeno, Junji ;

Hosono, Naoya ;

Takahashi, Atsushi ;

Kawaguchi, Takahisa ;

Matsumoto, Takayuki ;

Matsui, Toshiyuki ;

Kakuta, Yoichi ;

Kinouchi, Yoshitaka ;

Shimosegawa, Tooru ;

Hosokawa, Masayo ;

Arimura, Yoshiaki ;

Shinomura, Yasuhisa ;

Kiyohara, Yutaka ;

Tsunoda, Tatsuhiko ;

Kamatani, Naoyuki ;

Iida, Mitsuo ;

Nakamura, Yusuke ;

Kubo, Michiaki .

NATURE GENETICS, 2009, 41 (12) :1325-U92

[3] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[4] Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region [J].

Barrett, Jeffrey C. ;

Lee, James C. ;

Lees, Charles W. ;

Prescott, Natalie J. ;

Anderson, Carl A. ;

Phillips, Anne ;

Wesley, Emma ;

Parnell, Kirstie ;

Zhang, Hu ;

Drummond, Hazel ;

Nimmo, Elaine R. ;

Massey, Dunecan ;

Blaszczyk, Kasia ;

Elliott, Timothy ;

Cotterill, Lynn ;

Dallal, Helen ;

Lobo, Alan J. ;

Mowat, Craig ;

Sanderson, Jeremy D. ;

Jewell, Derek P. ;

Newman, William G. ;

Edwards, Cathryn ;

Ahmad, Tariq ;

Mansfield, John C. ;

Satsangi, Jack ;

Parkes, Miles ;

Mathew, Christopher G. ;

Donnelly, Peter ;

Peltonen, Leena ;

Blackwell, Jenefer M. ;

Bramon, Elvira ;

Brown, Matthew A. ;

Casas, Juan P. ;

Corvin, Aiden ;

Craddock, Nicholas ;

Deloukas, Panos ;

Duncanson, Audrey ;

Jankowski, Janusz ;

Markus, Hugh S. ;

McCarthy, Mark I. ;

Palmer, Colin N. A. ;

Plomin, Robert ;

Rautanen, Anna ;

Sawcer, Stephen J. ;

Samani, Nilesh ;

Trembath, Richard C. ;

Viswanathan, Ananth C. ;

Wood, Nicholas ;

Spencer, Chris C. A. ;

Bellenguez, Celine .

NATURE GENETICS, 2009, 41 (12) :1330-U99

[5] The Gene Ontology in 2010: extensions and refinements The Gene Ontology Consortium [J].

Berardini, Tanya Z. ;

Li, Donghui ;

Huala, Eva ;

Bridges, Susan ;

Burgess, Shane ;

McCarthy, Fiona ;

Carbon, Seth ;

Lewis, Suzanna E. ;

Mungall, Christopher J. ;

Abdulla, Amina ;

Wood, Valerie ;

Feltrin, Erika ;

Valle, Giorgio ;

Chisholm, Rex L. ;

Fey, Petra ;

Gaudet, Pascale ;

Kibbe, Warren ;

Basu, Siddhartha ;

Bushmanova, Yulia ;

Eilbeck, Karen ;

Siegele, Deborah A. ;

McIntosh, Brenley ;

Renfro, Daniel ;

Zweifel, Adrienne ;

Hu, James C. ;

Ashburner, Michael ;

Tweedie, Susan ;

Alam-Faruque, Yasmin ;

Apweiler, Rolf ;

Auchinchloss, Andrea ;

Bairoch, Amos ;

Barrell, Daniel ;

Binns, David ;

Blatter, Marie-Claude ;

Bougueleret, Lydie ;

Boutet, Emmanuel ;

Breuza, Lionel ;

Bridge, Alan ;

Browne, Paul ;

Chan, Wei Mun ;

Coudert, Elizabeth ;

Daugherty, Louise ;

Dimmer, Emily ;

Eberhardt, Ruth ;

Estreicher, Anne ;

Famiglietti, Livia ;

Ferro-Rojas, Serenella ;

Feuermann, Marc ;

Foulger, Rebecca ;

Gruaz-Gumowski, Nadine .

NUCLEIC ACIDS RESEARCH, 2010, 38 :D331-D335

[6] Induction and effector functions of TH17 cells [J].

Bettelli, Estelle ;

Korn, Thomas ;

Oukka, Mohamed ;

Kuchroo, Vijay K. .

NATURE, 2008, 453 (7198) :1051-1057

[7] A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals [J].

Browning, Brian L. ;

Browning, Sharon R. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (02) :210-223

[8] Diametrical clustering for identifying anti-correlated gene clusters [J].

Dhillon, IS ;

Marcotte, EM ;

Roshan, U .

BIOINFORMATICS, 2003, 19 (13) :1612-1619

[9] An insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases [J].

Dideberg, Vinciane ;

Kristjansdottir, Gudlaug ;

Milani, Lili ;

Libioulle, Cecile ;

Sigurdsson, Snaevar ;

Louis, Edouard ;

Wiman, Ann-Christin ;

Vermeire, Severine ;

Rutgeerts, Paul ;

Belaiche, Jacques ;

Franchimont, Denis ;

Van Gossum, Andre ;

Bours, Vincent ;

Syvanen, Ann-Christine .

HUMAN MOLECULAR GENETICS, 2007, 16 (24) :3008-3016

[10] Multiple common variants for celiac disease influencing immune gene expression [J].

Dubois, Patrick C. A. ;

Trynka, Gosia ;

Franke, Lude ;

Hunt, Karen A. ;

Romanos, Jihane ;

Curtotti, Alessandra ;

Zhernakova, Alexandra ;

Heap, Graham A. R. ;

Adany, Roza ;

Aromaa, Arpo ;

Bardella, Maria Teresa ;

van den Berg, Leonard H. ;

Bockett, Nicholas A. ;

de la Concha, Emilio G. ;

Dema, Barbara ;

Fehrmann, Rudolf S. N. ;

Fernandez-Arquero, Miguel ;

Fiatal, Szilvia ;

Grandone, Elvira ;

Green, Peter M. ;

Groen, Harry J. M. ;

Gwilliam, Rhian ;

Houwen, Roderick H. J. ;

Hunt, Sarah E. ;

Kaukinen, Katri ;

Kelleher, Dermot ;

Korponay-Szabo, Ilma ;

Kurppa, Kalle ;

MacMathuna, Padraic ;

Maki, Markku ;

Mazzilli, Maria Cristina ;

McCann, Owen T. ;

Mearin, M. Luisa ;

Mein, Charles A. ;

Mirza, Muddassar M. ;

Mistry, Vanisha ;

Mora, Barbara ;

Morley, Katherine I. ;

Mulder, Chris J. ;

Murray, Joseph A. ;

Nunez, Concepcion ;

Oosterom, Elvira ;

Ophoff, Roel A. ;

Polanco, Isabel ;

Peltonen, Leena ;

Platteel, Mathieu ;

Rybak, Anna ;

Salomaa, Veikko ;

Schweizer, Joachim J. ;

Sperandeo, Maria Pia .

NATURE GENETICS, 2010, 42 (04) :295-U42

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