Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation

underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan1, comprising, in

aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10−5. Seven of these

loci exceeded genome-wide significance (P < 5 × 10−8). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were

shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.

In the version of this article initially published, Kathryn Roeder's affiliation was incorrect. Her correct affiliation is the Department of Statistics, Carnegie Mellon University,

Pittsburgh, Pennsylvania, USA. The error has been corrected in the HTML and PDF versions of the article.

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

This study was supported in part by US National Center for Research Resources (NCRR) grant M01-RR00425 to the Cedars-Sinai General Research Center Genotyping core; US National Institutes of

Health/NIDDK grant P01-DK046763; Diabetes Endocrinology Research Center grant DK063491; Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. Additional funding was provided

by grants DK76984 (M.C.D.) and DK084554 (M.C.D. and D.P.B.M.). Cardiovascular Health Study 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 and N01-HC-45133; grant numbers U01 HL080295 and R01 HL087652 from the US National Heart, Lung, and Blood Institute; and

additional contribution from the US National Institute of Neurological Disorders and Stroke. A full list of principal Cardiovascular Health Study investigators and institutions can be found

at http://www.chs-nhlbi.org/pi.htm. A.G. is supported by the Crohn's and Colitis Foundation of America. R.J.X. and M.J.D. are supported by grants DK83756, DK086502 and DK043351 (NIDDK).

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.B.M.) and

DK062429 (J.H.C.). J.H.C. is also funded by Bohmfalk Funds for Medical Research, Burroughs Wellcome Medical Foundation and the Crohn's and Colitis Foundation of America. J.D.R. is also

funded by grants from the US National Institute of Allergy and Infectious Diseases (AI065687; AI067152) and from the US National Institute of Diabetes and Digestive and Kidney Diseases

(DK064869).

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

Singapore National Cancer Centre, Singapore General Hospital and the Singapore Millennium Foundation (to S.P.) and the Agency for Science Technology and Research (A*STAR), Singapore (to

M.L.H. and M.S.). Genotyping and DNA handling at the Genome Institute of Singapore were performed by W.Y. Meah, K.K. Heng, H.B. Toh, X. Lin, S. Rajaram, D. Tan and C.H. Wong. We are grateful

to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals.

Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

Dermot P B McGovern, Phillip R Fleshner, Marla C Dubinsky, Andy Ippoliti, Gil Y Melmed, Eric A Vasiliauskas & Stephan R Targan

Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Department for Clinical Science Intervention and Technology, Karolinska Institutet and IBD Clinical Research Group at Karolinska University Hospital, Stockholm, Sweden

Université de Montréal and the Montreal Heart Institute, Research Center, Montréal, Québec, Canada

Philippe Goyette, Caroline Lagacé, Claudine Beauchamp & John D Rioux

Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

Todd Green, Christine R Stevens, Ramnik J Xavier & Mark J Daly

Department of Medical Sciences, Gastroenterology Research Group, Uppsala University Hospital, Uppsala, Sweden

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden

Infectious Diseases, Genome Institute of Singapore, Singapore

Department of Medicine, and IBD Clinical Research Group at Karolinska University Hospital, Stockholm, Sweden

Department of Medicine, Rheumatology Unit, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden

Gastroenterologia ed Endoscopia Digestiva, Ospedale 'Casa Sollievo della Sofferenza', Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy

Angelo Andriulli, Elisabetta Colombo, Anna Latiano, Orazio Palmieri & Vito Annese

Université de Montréal and Centre Hospitalier Universitaire de l'Université de Montréal, Montréal, Québec, Canada

Department of Gastroenterology, Hôpital Sainte-Justine, Montréal, Québec, Canada

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands

Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Department of Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut, USA

Mount Sinai Hospital Inflammatory Bowel Disease Group, University of Toronto, Toronto, Ontario, Canada

Department of Genetics, Yale University, New Haven, Connecticut, USA

Department of Statistics, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA

Department of Medicine, Department of Epidemiology, Johns Hopkins University School of Medicine, and Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

Department of Health Studies, University of Chicago, Chicago, Illinois, USA

Division of Gastroenterology, Department of Medicine, and Department of Human Genetics, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Graduate School of Public

Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Departments of Epidemiology and General Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA

Department of Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands

Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Laboratory of Inflammation Biology, Singapore General Hospital, Singapore

Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA

Institute for Human Genetics, University of California San Fransisco, San Francisco, California, USA

D.P.B.M., M.J.D., R.J.X., J.D.R., J.H.C., P.G., R.H.D. and M.S. participated in the study design and conception. D.P.B.M., A.G., M.J.D., R.J.X., J.D.R. and M.S. wrote the manuscript with

contributions from R.H.D. and J.I.R. D.P.B.M., L.T., K.D.T., C.Li, C.B., P.R.F., M.C., M.D., J.H., M.L.H., M.L., L.P., A.A., E.C., A.L., O.P., E.-J.B., C.D., D.W.H., D.J.d.J., P.C.S.,

R.K.W., Y.S., M.S.S., J.H.C., S.R.B., L.P.S., R.H.D., M.C.D., N.L.G., T.H., A.I., G.Y.M., D.S.S., E.A.V., S.R.T., V.A., C.W. and S.P. performed patient diagnosis, patient enrollment and

collection of clinical data. Replication genotyping was performed by C. Lagacé, C.R.S. and C.B. in the laboratory of J.D.R. Expression analysis, immunohistochemistry and shRNA studies were

designed by A.G. and R.J.X. and performed by C. Li and A.G. M.J.D., J.E., B.M.N., K.R., J.W., J.D.R., P.G., T.G. and R.T.H.O. provided statistical analyses. All authors contributed to the

final paper.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Supplementary Tables 1–5 and Supplementary Figures 1 and 2 (PDF 2209 kb)

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