Abstract
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 × 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.
Original language | English (US) |
---|---|
Pages (from-to) | 246-252 |
Number of pages | 7 |
Journal | Nature genetics |
Volume | 43 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2011 |
Externally published | Yes |
ASJC Scopus subject areas
- Genetics
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In: Nature genetics, Vol. 43, No. 3, 03.2011, p. 246-252.
Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47
AU - Anderson, Carl A.
AU - Boucher, Gabrielle
AU - Lees, Charlie W.
AU - Franke, Andre
AU - D'Amato, Mauro
AU - Taylor, Kent D.
AU - Lee, James C.
AU - Goyette, Philippe
AU - Imielinski, Marcin
AU - Latiano, Anna
AU - Lagacé, Caroline
AU - Scott, Regan
AU - Amininejad, Leila
AU - Bumpstead, Suzannah
AU - Baidoo, Leonard
AU - Baldassano, Robert N.
AU - Barclay, Murray
AU - Bayless, Theodore M.
AU - Brand, Stephan
AU - Büning, Carsten
AU - Colombel, Jean Frédéric
AU - Denson, Lee A.
AU - De Vos, Martine
AU - Dubinsky, Marla
AU - Edwards, Cathryn
AU - Ellinghaus, David
AU - Fehrmann, Rudolf S.N.
AU - Floyd, James A.B.
AU - Florin, Timothy
AU - Franchimont, Denis
AU - Franke, Lude
AU - Georges, Michel
AU - Glas, Jürgen
AU - Glazer, Nicole L.
AU - Guthery, Stephen L.
AU - Haritunians, Talin
AU - Hayward, Nicholas K.
AU - Hugot, Jean Pierre
AU - Jobin, Gilles
AU - Laukens, Debby
AU - Lawrance, Ian
AU - Lémann, Marc
AU - Levine, Arie
AU - Libioulle, Cecile
AU - Louis, Edouard
AU - McGovern, Dermot P.
AU - Milla, Monica
AU - Montgomery, Grant W.
AU - Morley, Katherine I.
AU - Mowat, Craig
AU - Ng, Aylwin
AU - Newman, William
AU - Ophoff, Roel A.
AU - Papi, Laura
AU - Palmieri, Orazio
AU - Peyrin-Biroulet, Laurent
AU - Panés, Julián
AU - Phillips, Anne
AU - Prescott, Natalie J.
AU - Proctor, Deborah D.
AU - Roberts, Rebecca
AU - Russell, Richard
AU - Rutgeerts, Paul
AU - Sanderson, Jeremy
AU - Sans, Miquel
AU - Schumm, Philip
AU - Seibold, Frank
AU - Sharma, Yashoda
AU - Simms, Lisa A.
AU - Seielstad, Mark
AU - Steinhart, A. Hillary
AU - Targan, Stephan R.
AU - Van Den Berg, Leonard H.
AU - Vatn, Morten
AU - Verspaget, Hein
AU - Walters, Thomas
AU - Wijmenga, Cisca
AU - Wilson, David C.
AU - Westra, Harm Jan
AU - Xavier, Ramnik J.
AU - Zhao, Zhen Z.
AU - Ponsioen, Cyriel Y.
AU - Andersen, Vibeke
AU - Torkvist, Leif
AU - Gazouli, Maria
AU - Anagnou, Nicholas P.
AU - Karlsen, Tom H.
AU - Kupcinskas, Limas
AU - Sventoraityte, Jurgita
AU - Mansfield, John C.
AU - Kugathasan, Subra
AU - Silverberg, Mark S.
AU - Halfvarson, Jonas
AU - Rotter, Jerome I.
AU - Mathew, Christopher G.
AU - Griffiths, Anne M.
AU - Gearry, Richard
AU - Ahmad, Tariq
AU - Brant, Steven R.
AU - Chamaillard, Mathias
AU - Satsangi, Jack
AU - Cho, Judy H.
AU - Schreiber, Stefan
AU - Daly, Mark J.
AU - Barrett, Jeffrey C.
AU - Parkes, Miles
AU - Annese, Vito
AU - Hakonarson, Hakon
AU - Radford-Smith, Graham
AU - Duerr, Richard H.
AU - Vermeire, Séverine
AU - Weersma, Rinse K.
AU - Rioux, John D.
N1 - Funding Information: Replication genotyping was supported by unrestricted grants from Abbott Laboratories Ltd, Giuliani SpA, Shire PLC and Ferring Pharmaceuticals. We thank the 1958 British Birth Cohort and Banco Nacional deADN, Salamanca, Spain, who supplied control DNA samples. The IBSEN study group and the Norwegian Bone Marrow Donor Registry are acknowledged for contributing the Norwegian patient and control populations. The Cardiovascular Health Study (CHS) research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. We thank the members of the Quebec IBD Genetic Consortium, in particular A. Bitton, G. Aumais, E.J. Bernard, A. Cohen, C. Deslandres, R. Lahaie, D. Langelier and P. Paré. Other important contributors are K. Hanigan, N. Huang, P. Webb, D. Whiteman, A. Rutherford, R. Gwilliam, J. Ghori, D. Strachan, W. McCardle, W. Ouwehand, M. Newsky, S. Ehlers, I. Pauselius, K. Holm, C. Sina, M. Regueiro, A. Andriulli and M.C. Renda. Funding Information: In memoriam to Marc Lémann, who dedicated his life to his patients but died too soon. We thank all the subjects who contributed samples and the physicians and nursing staff who helped with recruitment globally. This study was supported by the German Ministry of Education and Research through the National Genome Research Network, the Popgen biobank and infrastructure support through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. Italian case collections were supported by the Italian Group for IBD and the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition. We acknowledge funding provided by the Royal Brisbane and Women’s Hospital Foundation, University of Queensland (Ferguson Fellowship), National Health and Medical Research Council, Australia and by the European Community (5th PCRDT). UK case collections were supported by the National Association for Colitis and Crohn’s disease, Wellcome Trust, Medical Research Council UK and Peninsular College of Medicine and Dentistry, Exeter. Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Agency for Science Technology and Research (A*STAR), Singapore. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. The Wellcome Trust Case Control Consortium 2 project was supported by Wellcome Trust grant 083948/Z/07/Z. We also acknowledge the National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy’s & St. Thomas’ National Health Service (NHS) Trust, King’s College London and to Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine and to the University of Manchester and Central Manchester Foundation Trust. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S.R.B.), DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), DK062423 (M.S.S.), DK062413 (D.P.M.), DK076984 (M.J.D.), DK084554 (M.J.D. and D.P.M.) and DK062429 (J.H.C.). J.H.C. is also funded by the Crohn’s and Colitis Foundation of America; S.L.G. by DK069513 and Primary Children’s Medical Center Foundation; and J.D.R. by US National Institutes of Health (NIH)/NIDDK grant DK064869. Cedars-Sinai is supported by National Center for Research Resources (NCRR) grant M01-RR00425, NIH/NIDDK grant P01-DK046763, DK 063491 and Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. E.L., D.F. and S.V. are senior clinical investigators for the Funds for Scientific Research (FWO/FNRS) Belgium. S. Brand was supported by Deutsche Forschungsgemeinschaft (DFG BR 1912/5-1) and Else Kröner-Fresenius-Stiftung (P50/05/EKMS05/62). M.C. was supported by the Programme Hospitalier de Recherche Clinique. C.A.A. is supported by Wellcome Trust grant WT091745/ Z/10/Z. J.C.B. is supported by Wellcome Trust grant WT089120/Z/09/Z. R.K.W. is supported by a clinical fellowship grant (90.700.281) from the Netherlands Organization for Scientific Research (NWO). C.W. is supported by grants from the Celiac Disease Consortium (BSIK03009) and The Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620). L.H.v.d.B. acknowledges funding from the Prinses Beatrix Fonds, the Adessium Foundation and the Amyotrophic Lateral Sclerosis Association. L.F. received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). R.J.X. and A.N. are funded by DK83756, AI062773, DK043351 and the Helmsley Foundation.
PY - 2011/3
Y1 - 2011/3
N2 - 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 × 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.
AB - 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 × 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.
UR - http://www.scopus.com/inward/record.url?scp=79952195585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952195585&partnerID=8YFLogxK
U2 - 10.1038/ng.764
DO - 10.1038/ng.764
M3 - Review article
C2 - 21297633
AN - SCOPUS:79952195585
SN - 1061-4036
VL - 43
SP - 246
EP - 252
JO - Nature genetics
JF - Nature genetics
IS - 3
ER -