Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

被引：2009

作者：

Franke, Andre ^{[2
]}

McGovern, Dermot P. B. ^{[3
,4
]}

Barrett, Jeffrey C. ^{[5
]}

Wang, Kai ^{[6
]}

Radford-Smith, Graham L. ^{[7
]}

Ahmad, Tariq ^{[8
]}

Lees, Charlie W. ^{[9
]}

Balschun, Tobias ^{[10
]}

Lee, James ^{[1
]}

Roberts, Rebecca ^{[11
]}

Anderson, Carl A. ^{[5
]}

Bis, Joshua C. ^{[12
]}

Bumpstead, Suzanne ^{[5
]}

Ellinghaus, David ^{[2
]}

Festen, Eleonora M. ^{[13
]}

Georges, Michel ^{[14
]}

Green, Todd ^{[15
]}

Haritunians, Talin ^{[4
]}

Jostins, Luke ^{[5
]}

Latiano, Anna ^{[16
]}

Mathew, Christopher G. ^{[17
]}

Montgomery, Grant W.

Prescott, Natalie J. ^{[17
]}

Raychaudhuri, Soumya ^{[15
]}

Rotter, Jerome I. ^{[4
]}

Schumm, Philip ^{[18
]}

Sharma, Yashoda ^{[19
]}

Simms, Lisa A. ^{[7
]}

Taylor, Kent D. ^{[4
]}

Whiteman, David

Wijmenga, Cisca ^{[13
]}

Baldassano, Robert N. ^{[20
]}

Barclay, Murray ^{[11
]}

Bayless, Theodore M. ^{[21
]}

Brand, Stephan ^{[22
]}

Buening, Carsten ^{[23
]}

Cohen, Albert ^{[24
]}

Colombel, Jean-Frederick ^{[25
]}

Cottone, Mario ^{[26
]}

Stronati, Laura ^{[27
]}

Denson, Ted ^{[28
]}

De Vos, Martine ^{[29
]}

D'Inca, Renata ^{[30
]}

Dubinsky, Marla ^{[31
]}

Edwards, Cathryn ^{[32
]}

Florin, Tim ^{[33
]}

Franchimont, Denis ^{[34
]}

Gearry, Richard ^{[11
]}

Glas, Juergen ^{[22
,35
,36
]}

Van Gossum, Andre ^{[34
]}

机构：

[1] Univ Cambridge, Inflammatory Bowel Dis Res Grp, Cambridge, England

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

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

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

[5] Wellcome Trust Sanger Inst, Cambridge, England

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

[7] Queensland Inst Med Res, Inflammatory Bowel Dis Res Grp, Brisbane, Qld 4006, Australia

[8] Peninsula Coll Med & Dent, Exeter, Devon, England

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

[10] Univ Kiel, PopGen Biobank, Kiel, Germany

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

[12] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

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

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

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

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

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

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

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

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

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

[22] Univ Munich, Dept Med 2, Univ Hosp Munich Grosshadern, Munich, Germany

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

[24] Montreal Jewish Gen Hosp, Montreal, PQ, Canada

[25] Univ Lille, Registre Malad Inflammatoires Tube Digestif Nord, Lille, France

[26] Cervello Hosp, Gastroenterol Unit, Palermo, Italy

[27] Agenzia Nazl Nuove Tecnol Energia Sviluppo Econ S, Dept Biol Radiat & Human Hlth, Rome, Italy

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

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

[30] Univ Hosp Padua, Div Gastroenterol, Padua, Italy

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

[32] Torbay Hosp, Torquay, Avon, England

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

[34] Free Univ Brussels, Erasme Hosp, Dept Gastroenterol, B-1050 Brussels, Belgium

[35] Univ Munich, Dept Prevent Dent & Periodontol, Munich, Germany

[36] Rhein Westfal TH Aachen, Dept Human Genet, Aachen, Germany

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

[38] Orebro Univ Hosp, Dept Med, Orebro, Sweden

[39] Leiden Univ, Med Ctr, Dept Gastroenterol, Leiden, Netherlands

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

[41] Technion Israel Inst Technol, Fac Med, Dept Gastroenterol, Haifa, Israel

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

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

[44] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel

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

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

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

[48] Hosp Clin Barcelona, Dept Gastroenterol, CIBER EHD, IDIBAPS, Barcelona, Spain

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

[50] Yorkhill Hosp, Dept Paediat Gastroenterol, Glasgow, Lanark, Scotland

来源：

NATURE GENETICS | 2010年 / 42卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

INFLAMMATORY-BOWEL-DISEASE; SEQUENCE VARIANTS; COMMON VARIANTS; NEDD4; FAMILY; ASSOCIATION; GENE; IDENTIFICATION; ACTIVATION; CONTRIBUTE; AUTOPHAGY;

D O I：

10.1038/ng.717

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

引用

页码：1118 / +

页数：9

共 52 条

[11] Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource [J].

Dendrou, Calliope A. ;

Plagnol, Vincent ;

Fung, Erik ;

Yang, Jennie H. M. ;

Downes, Kate ;

Cooper, Jason D. ;

Nutland, Sarah ;

Coleman, Gillian ;

Himsworth, Matthew ;

Hardy, Matthew ;

Burren, Oliver ;

Healy, Barry ;

Walker, Neil M. ;

Koch, Kerstin ;

Ouwehand, Willem H. ;

Bradley, John R. ;

Wareham, Nicholas J. ;

Todd, John A. ;

Wicker, Linda S. .

NATURE GENETICS, 2009, 41 (09) :1011-U80

[12] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[13] A genome-wide association study identifies IL23R as an inflammatory bowel disease gene [J].

Duerr, Richard H. ;

Taylor, Kent D. ;

Brant, Steven R. ;

Rioux, John D. ;

Silverberg, Mark S. ;

Daly, Mark J. ;

Steinhart, A. Hillary ;

Abraham, Clara ;

Regueiro, Miguel ;

Griffiths, Anne ;

Dassopoulos, Themistocles ;

Bitton, Alain ;

Yang, Huiying ;

Targan, Stephan ;

Datta, Lisa Wu ;

Kistner, Emily O. ;

Schumm, L. Philip ;

Lee, Annette T. ;

Gregersen, Peter K. ;

Barmada, M. Michael ;

Rotter, Jerome I. ;

Nicolae, Dan L. ;

Cho, Judy H. .

SCIENCE, 2006, 314 (5804) :1461-1463

[14] G9a and HP1 Couple Histone and DNA Methylation to TNFα Transcription Silencing during Endotoxin Tolerance [J].

El Gazzar, Mohamed ;

Yoza, Barbara K. ;

Chen, Xiaoping ;

Hu, Jean ;

Hawkins, Gregory A. ;

Mccall, Charles E. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (47) :32198-32208

[15] Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility [J].

Franke, Andre ;

Balschun, Tobias ;

Karlsen, Tom H. ;

Sventoraityte, Jurgita ;

Nikolaus, Susanna ;

Mayr, Gabriele ;

Domingues, Francisco S. ;

Albrecht, Mario ;

Nothnagel, Michael ;

Ellinghaus, David ;

Sina, Christian ;

Onnie, Clive M. ;

Weersma, Rinse K. ;

Stokkers, Pieter C. F. ;

Wijmenga, Cisca ;

Gazouli, Maria ;

Strachan, David ;

McArdle, Wendy L. ;

Vermeire, Severine ;

Rutgeerts, Paul ;

Rosenstiel, Philip ;

Krawczak, Michael ;

Vatn, Morten H. ;

Mathew, Christopher G. ;

Schreiber, Stefan .

NATURE GENETICS, 2008, 40 (11) :1319-1323

[16]

Fried Linda P., 1991, Annals of Epidemiology, V1, P263

[17] Identification of DNA Methyltransferase 3a as a T Cell Receptor-Induced Regulator of Th1 and Th2 Differentiation [J].

Gamper, Christopher J. ;

Agoston, Agoston T. ;

Nelson, William G. ;

Powell, Jonathan D. .

JOURNAL OF IMMUNOLOGY, 2009, 183 (04) :2267-2276

[18] Janus kinases in immune cell signaling [J].

Ghoreschi, Kamran ;

Laurence, Arian ;

O'Shea, John J. .

IMMUNOLOGICAL REVIEWS, 2009, 228 :273-287

[19] Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor [J].

Glocker, Erik-Oliver ;

Kotlarz, Daniel ;

Boztug, Kaan ;

Gertz, E. Michael ;

Schaeffer, Alejandro A. ;

Noyan, Fatih ;

Perro, Mario ;

Diestelhorst, Jana ;

Allroth, Anna ;

Murugan, Dhaarini ;

Haetscher, Nadine ;

Pfeifer, Dietmar ;

Sykora, Karl-Walter ;

Sauer, Martin ;

Kreipe, Hans ;

Lacher, Martin ;

Nustede, Rainer ;

Woellner, Cristina ;

Baumann, Ulrich ;

Salzer, Ulrich ;

Koletzko, Sibylle ;

Shah, Neil ;

Segal, Anthony W. ;

Sauerbrey, Axel ;

Buderus, Stephan ;

Snapper, Scott B. ;

Grimbacher, Bodo ;

Klein, Christoph .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (21) :2033-2045

[20] N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel golgi-associated protein [J].

Harvey, KF ;

Shearwin-Whyatt, LM ;

Fotia, A ;

Parton, RG ;

Kumar, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (11) :9307-9317

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