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Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study

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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Figure 1: Association signals and recombination rates for loci showing genome-wide significant association with UC.

Change history

  • 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.).

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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.

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Correspondence to Richard H Duerr.

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Silverberg, M., Cho, J., Rioux, J. et al. Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet 41, 216–220 (2009).

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