Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 (original) (raw)
Change history
11 August 2011
In the version of this article initially published, an affiliation was missing for two authors, Maria Gazouli and Nicholas P. Anagnou. They are also affiliated with the Foundation for Biomedical Research of the Academy of Athens in Athens, Greece. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
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.
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.
Author information
Author notes
- Gabrielle Boucher, Charlie W Lees, Andre Franke and Mauro D'Amato: These authors contributed equally to this work.
- Hakon Hakonarson, Graham Radford-Smith, Richard H Duerr, Séverine Vermeire and Rinse K Weersma: These authors jointly supervised this work.
Authors and Affiliations
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
Carl A Anderson, Suzannah Bumpstead, James A B Floyd, Katherine I Morley & Jeffrey C Barrett - Université de Montréal, Medicine, Montréal, Québec, Canada
Gabrielle Boucher, Philippe Goyette, Caroline Lagacé, Gilles Jobin & John D Rioux - Montreal Heart Institute, Research Center, Montréal, Québec, Canada
Gabrielle Boucher, Philippe Goyette, Caroline Lagacé & John D Rioux - University of Edinburgh, Western General Hospital, Gastrointestinal Unit, Molecular Medicine Centre, Edinburgh, UK
Charlie W Lees & Jack Satsangi - Christian-Albrechts-University Kiel, Institute of Clinical Molecular Biology, Kiel, Germany
Andre Franke, David Ellinghaus & Stefan Schreiber - Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden
Mauro D'Amato - Cedars-Sinai Medical Center, Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California, USA
Kent D Taylor, Dermot P McGovern & Stephan R Targan - Addenbrooke's Hospital, University of Cambridge, Gastroenterology Research Unit, Cambridge, UK
James C Lee & Miles Parkes - The Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, USA
Marcin Imielinski - Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, San Giovanni Rotondo, Italy
Anna Latiano, Orazio Palmieri & Vito Annese - Division of Gastroenterology, Department of Medicine, University of Pittsburgh School of Medicine, Hepatology and Nutrition, Pittsburgh, Pennsylvania, USA
Regan Scott, Leonard Baidoo & Richard H Duerr - Department of Gastroenterology, Erasmus Hospital, Free University of Brussels, Brussels, Belgium
Leila Amininejad - Department of Pediatrics, The Children's Hospital of Philadelphia, Center for Pediatric Inflammatory Bowel Disease, Philadelphia, Pennsylvania, USA
Robert N Baldassano & Hakon Hakonarson - Department of Medicine, University of Otago, Christchurch, New Zealand
Murray Barclay, Rebecca Roberts & Richard Gearry - Department of Medicine, Johns Hopkins University School of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Baltimore, Maryland, USA
Theodore M Bayless & Steven R Brant - Department of Medicine II, University Hospital Munich, Munich, Germany
Stephan Brand & Jürgen Glas - Department of Gastroenterology, Universitätsmedizin Berlin, Charité, Campus Mitte, Berlin, Germany
Carsten Büning - Université de Lille Department of Hepato-Gastroenterology, Lille, France
Jean-Frédéric Colombel - Cincinnati Children's Hospital Medical Center, Pediatric Gastroenterology, Cincinnati, Ohio, USA
Lee A Denson - Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
Martine De Vos & Debby Laukens - Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California, USA
Marla Dubinsky - Department of Gastroenterology, Torbay Hospital, Torbay, Devon, UK
Cathryn Edwards - Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands
Rudolf S N Fehrmann, Lude Franke, Cisca Wijmenga & Harm-Jan Westra - Department of Gastroenterology, Mater Health Services, Brisbane, Australia
Timothy Florin - Department of Gastroenterology, Erasmus Hospital, Free University of Brussels, Brussels, Belgium
Denis Franchimont - Department of Genetics, University of Liège, Faculty of Veterinary Medicine, Liège, Belgium
Michel Georges - Department of Internal Medicine, University of Washington, Cardiovascular Health Research Unit, Seattle, Washington, USA
Nicole L Glazer - Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA
Stephen L Guthery - Cedars-Sinai Medical Center, Medical Genetics Institute, Los Angeles, California, USA
Talin Haritunians, Dermot P McGovern & Jerome I Rotter - Queensland Institute of Medical Research, Oncogenomics Laboratory, Brisbane, Australia
Nicholas K Hayward - Université Paris Diderot, Paris, France
Jean-Pierre Hugot - Department of Gastroenterology, Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada
Gilles Jobin - The University of Western Australia, School of Medicine and Pharmacology, Fremantle, Australia
Ian Lawrance - Université Paris Diderot, GETAID group, Paris, France
Marc Lémann - Tel Aviv University, Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv, Israel
Arie Levine - Division of Gastroenterology, Centre Hospitalier Universitaire Université de Liège, Liège, Belgium
Cecile Libioulle & Edouard Louis - Azienda Ospedaliero Universitaria (AOU) Careggi, Unit of Gastroenterology SOD2, Florence, Italy
Monica Milla & Vito Annese - Queensland Institute of Medical Research, Molecular Epidemiology, Brisbane, Australia
Grant W Montgomery & Zhen Z Zhao - Department of Medicine, Ninewells Hospital and Medical School, Dundee, UK
Craig Mowat & Anne Phillips - Massachusetts General Hospital, Harvard Medical School, Gastroenterology Unit, Boston, Massachusetts, USA
Aylwin Ng & Ramnik J Xavier - Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
Aylwin Ng & Ramnik J Xavier - University of Manchester Department of Medical Genetics, Manchester, UK
William Newman - Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
Roel A Ophoff - University of Florence, Institute of Human Genetics, Florence, Italy
Laura Papi - Department of Hepato-Gastroenterology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
Laurent Peyrin-Biroulet - Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
Julián Panés - Department of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital, London, UK
Natalie J Prescott & Christopher G Mathew - Department of Medicine, Yale University, Section of Digestive Diseases, New Haven, Connecticut, USA
Deborah D Proctor, Yashoda Sharma & Judy H Cho - Royal Hospital for Sick Children, Paediatric Gastroenterology and Nutrition, Glasgow, UK
Richard Russell & David C Wilson - Division of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
Paul Rutgeerts & Séverine Vermeire - Department of Gastroenterology, Guy's & St. Thomas' NHS Foundation Trust, St. Thomas' Hospital, London, UK
Jeremy Sanderson - Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
Miquel Sans - Department of Health Studies, University of Chicago, Chicago, Illinois, USA
Philip Schumm - Division of Gastroenterology, University of Bern, Inselspital, Bern, Switzerland
Frank Seibold - Queensland Institute of Medical Research, Inflammatory Bowel Diseases, Brisbane, Australia
Lisa A Simms & Graham Radford-Smith - Genome Institute of Singapore, Human Genetics, Singapore
Mark Seielstad - Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA
Mark Seielstad - University of Toronto, Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, Canada
A Hillary Steinhart & Mark S Silverberg - Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
Leonard H van den Berg - Medical Department, Rikshospitalet University Hospital, Oslo, Norway
Morten Vatn & Tom H Karlsen - Leiden University Medical Center, Experimental Gastroenterology, Leiden, The Netherlands
Hein Verspaget - The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Thomas Walters & Anne M Griffiths - Child Life and Health, University of Edinburgh, Edinburgh, Scotland, UK
David C Wilson - Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands
Cyriel Y Ponsioen - Medical Department, Viborg Regional Hospital, Viborg, Denmark
Vibeke Andersen - Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Leif Torkvist - Department of Biology, University of Athens, School of Medicine, Athens, Greece
Maria Gazouli & Nicholas P Anagnou - Foundation for Biomedical Research of the Academy of Athens,, Athens, Greece
Maria Gazouli & Nicholas P Anagnou - Department of Gastroenterology, Kaunas University of Medicine, Kaunas, Lithuania
Limas Kupcinskas & Jurgita Sventoraityte - Newcastle University, Institute of Human Genetics, Newcastle upon Tyne, UK
John C Mansfield - Department of Genetics and Department of Pediatrics, Emory School of Medicine, Atlanta, Georgia, USA
Subra Kugathasan - Department of Medicine, Örebro University Hospital, Örebro, Sweden
Jonas Halfvarson - Peninsula College of Medicine and Dentistry, Barrack Road, Exeter, UK
Tariq Ahmad - INSERM, U1019, Lille, France
Mathias Chamaillard - Department of Genetics, Yale University, Yale School of Medicine, New Haven, Connecticut, USA
Judy H Cho - Department for General Internal Medicine, Christian-Albrechts-University, Kiel, Germany
Stefan Schreiber - Massachusetts General Hospital, Harvard Medical School, Center for Human Genetic Research, Boston, Massachusetts, USA
Mark J Daly - Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Hakon Hakonarson - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
Richard H Duerr - Department of Gastroenterology, University Medical Center Groningen, Groningen, The Netherlands
Rinse K Weersma
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Contributions
C.W.L., A.F., K.D.T., J.C.L., M.I., A. Latiano, L.A., L.B., R.N.B., M.B., T.M.B., S. Brand, C.B., J.-F.C., L.A.D., M.D.V., M.D., C.E., R.S.N.F., T.F., D.F., M. Georges, J.G., N.L.G., S.L.G., T.H., N.K.H., J.-P.H., G.J., D.L., I.L., M.L., A. Levine, C. Libioulle, E.L., D.P.M., M.M., C.M., A.N., W.N., R.A.O., L.P., O.P., L.P.-B., J.P., A.P., N.J.P., D.D.P., R. Roberts, R. Russell, P.R., J. Sanderson, M. Sans, P.S., F.S., Y.S., M. Seielstad, A.H.S., S.R.T., L.H.v.d.B., M.V., H.V., T.W., C.W., D.C.W., H.-J.W., C.Y.P., V. Andersen, L.T., M. Gazouli, N.P.A., T.H.K., L.K., J. Sventoraityte, J.C.M., S.K., M.S.S., J.H., J.I.R., C.G.M., A.M.G., R.G., T.A., S.R.B., M.C., J. Satsangi, J.H.C., S.S., M.P., V. Annese, H.H., G.R.-S., R.H.D., S.V., R.K.W. and J.D.R. established DNA collections, recruited patients or assembled phenotypic data. A.F., M.D., P.G., C. Lagacé, R.S., S. Bumpstead, C. Libioulle, D.P.M., G.W.M., L.A.S., Z.Z.Z., M.C., R.H.D. and J.D.R. conducted or supervised laboratory work. C.A.A., G.B., D.E., J.A.B.F., L.F., K.I.M., A.N., R.A.O., R.J.X., M.J.D., J.C.B., R.K.W. and J.D.R. performed or supervised statistical analyses. C.A.A., G.B., C.W.L., G.R.-S., R.H.D., S.V., R.K.W. and J.D.R. drafted the manuscript. All authors read and approved the final manuscript before submission.
Corresponding authors
Correspondence toCarl A Anderson or John D Rioux.
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The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Tables 1, 2, 4–6 and 8 and Supplementary Figures 1–3. (PDF 3143 kb)
Supplementary Table 3a
Cohort specific results for all SNPs listed in Table 1 and Table 2 (XLSX 63 kb)
Supplementary Table 3b
Cohort specific results for all SNPs included in follow-up phase, but failed our thresholds for follow-up (XLSX 38 kb)
Supplementary Table 7
Summary of candidate genes mapping from in silico analysis on the 47 UC loci (XLSX 13 kb)
Supplementary Table 9
Results from the International IBD Genetics Consortium CD and UC meta-analyses for the 99 loci reported for association in CD and/or UC (XLSX 37 kb)
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Anderson, C., Boucher, G., Lees, C. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.Nat Genet 43, 246–252 (2011). https://doi.org/10.1038/ng.764
- Received: 15 September 2010
- Accepted: 14 January 2011
- Published: 06 February 2011
- Issue Date: March 2011
- DOI: https://doi.org/10.1038/ng.764