• A Corrigendum to this article was published on 01 June 2009

This article has been updated


Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 × 10−13, combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 × 10−12, combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 × 10−16, combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 × 10−8, combined OR = 0.56; rs10889677, combined P = 1.3 × 10−8, combined OR = 1.29).

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  • 28 April 2009

    NOTE: In the first paragraph of the second column on the third page, rs11209026 A allele was incorrectly listed as rs111209026 A allele. The error has been corrected in the HTML and PDF versions of the article.


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Thanks to L. Wu Datta, J. Fultz and J. Stempak for coordinating study subject recruitment, to A. Andriulli and O. Palmieri for providing clinical data and to J. Lian, A. Liew and H. Khalili for technical support. 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 (K.D.T.) and DK062429 (J.H.C.). The authors would also like to acknowledge additional support from the Atran Foundation (S.R.B.), Board of Governor's Chair in Medical Genetics at Cedars-Sinai Medical Center (J.I.R.), Bohmfalk Funds for Medical Research (J.H.C.), Burroughs Wellcome Medical Foundation (J.H.C.), Crohn's and Colitis Foundation of America (C.A., T.M.B., S.R.B., J.H.C., R.H.D., J.D.R.), Crohn's and Colitis Foundation of Canada (M.S.S.), Feintech Chair in Immunobiology (S.R.T.), Gale and Graham Wright Research Chair in Digestive Diseases (M.S.S.), Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center (T.M.B., S.R.B.), US National Institutes of Health grants RR00052 (S.R.B.), DK077905 (C.A.), DK068112 (J.-P.A.), DK072373 (J.H.C.), RR024139 (J.H.C.), DK076025 (R.H.D.), DK064869 (J.D.R.), MH057881 (K.R.), DK046763 (J.I.R., S.R.T., K.D.T.) and RR00425 (K.D.T.), the Rainin IBD Genetics Research Fund (J.-P.A.) and the W. Buford Lewis family (S.R.B.).

Author information

Author notes

    • Mark S Silverberg
    •  & Judy H Cho

    These authors contributed equally to this work


  1. Mount Sinai Hospital Inflammatory Bowel Disease Group, University of Toronto, 600 University Avenue, Toronto, ON M5G1X5, Canada

    • Mark S Silverberg
    •  & A Hillary Steinhart
  2. Section of Digestive Diseases, Department of Medicine, Yale University, 333 Cedar Street, LMP1080, New Haven, Connecticut 06520, USA

    • Judy H Cho
    • , Clara Abraham
    •  & Deborah D Proctor
  3. Department of Genetics, Yale University, 333 Cedar Street, LMP1080, New Haven, Connecticut 06520, USA

    • Judy H Cho
  4. Université de Montréal and the Montreal Heart Institute, Research Center, 5000 rue Belanger, Montréal, QC H1T1C8, Canada

    • John D Rioux
    •  & Philippe Goyette
  5. Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA

    • Dermot P B McGovern
    • , Andrew F Ippoliti
    • , Stephan R Targan
    • , Jerome I Rotter
    •  & Kent D Taylor
  6. Department of Statistics, Carnegie Mellon University, Baker/Porter Hall A60K, Pittsburgh, Pennsylvania 15213, USA

    • Jing Wu
    •  & Kathryn Roeder
  7. IRCCS-CSS Hospital, Viale Cappuccini, 1, S. Giovanni Rotondo, Fg 71013, Italy

    • Vito Annese
    • , Fabrizio Bossa
    •  & Anna Latiano
  8. Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A31, Cleveland, Ohio 44195, USA

    • Jean-Paul Achkar
  9. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, UPMC-PUH, Mezzanine Level, C-Wing, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA

    • Regan Scott
    • , Miguel D Regueiro
    •  & Richard H Duerr
  10. Princess Margaret Hospital, Department of Public Health Sciences, University of Toronto, 610 University Avenue, Toronto, ON M5G2M9, Canada

    • Wei Xu
  11. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA

    • M Michael Barmada
    •  & Richard H Duerr
  12. University of Pittsburgh Medical Center, Department of Psychiatry, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, USA

    • Lambertus Klei
  13. Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA

    • Mark J Daly
  14. Johns Hopkins University School of Medicine, Department of Medicine, Harvey M. and Lyn P. Meyerhoff Infammatory Bowel Disease Center, 600 N. Wolfe Street, Baltimore, Maryland 21287, USA

    • Theodore M Bayless
    •  & Steven R Brant
  15. The Hospital for Sick Children, Department of Pediatrics, 555 University Avenue, Toronto, ON M5G1X8, Canada

    • Anne M Griffiths
  16. Department of Medicine, Université de Montréal and CHUM–Hôpital Saint-Luc, 1058, rue Saint-Denis, Montréal, QC H2X3J4, Canada

    • Raymond G Lahaie
  17. Division of Gastroenterology, Department of Medicine, Laval University, Quebec City, CHAUQ–Hôpital du St-Sacrement, 1050, Chemin Ste–Foy, QC G1S4L8, Canada

    • Pierre Paré
  18. Department of Health Studies, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA

    • L Philip Schumm
    •  & Emily O Kistner
  19. The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA

    • Annette T Lee
    •  & Peter K Gregersen
  20. Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA

    • Jerome I Rotter
    •  & Kent D Taylor
  21. Johns Hopkins University Bloomberg School of Public Health, Department of Epidemiology, 1501 E. Jefferson Street, B136, Baltimore, Maryland 21231, USA

    • Steven R Brant


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J.H.C., E.O.K. and L.P.S. developed and maintained the US National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) IBD Genetics Consortium Data Coordinating Center infrastructure. C.A., J.-P.A., V.A., T.M.B., F.B., S.R.B., J.H.C., R.H.D., A.M.G., A.F.I., R.G.L., A.L., D.P.B.M., P.P., D.D.P., M.D.R., J.D.R., J.I.R., R.S., M.S.S., A.H.S., S.R.T. and K.D.T. provided clinical samples and information. S.R.B., J.H.C., M.J.D., R.H.D., P.K.G., A.T.L., J.D.R., J.I.R., M.S.S. and K.D.T. designed the GWAS. M.M.B. and R.H.D. performed quality control and preliminary association analyses of the GWAS data. J.W. performed the GEM, quantile-quantile and conditional analyses of the GWAS data under the supervision of K.R., with contributions from L.K. M.J.D. defined the 'best region' SNPs among SNPs with GWAS P < 0.0001. W.X. identified the best GWAS proxies for CD and UC loci. R.H.D., P.G., J.D.R. and R.S. designed and performed the replication study. R.H.D. and P.G. analyzed the replication data. The manuscript was written by J.H.C., R.H.D., K.R. and M.S.S. with contributions from C.A., M.M.B., S.R.B., P.K.G., D.P.B.M., J.D.R., J.I.R., R.S. and J.W. R.H.D. coordinated the genotyping, analysis and manuscript writing efforts of this multicenter study.

Corresponding author

Correspondence to Richard H Duerr.

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