Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease (original) (raw)

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Acknowledgements

We acknowledge use of DNA from the 1958 British Birth Cohort collection (R. Jones, S. Ring, W. McArdle and M. Pembrey), funded by the Medical Research Council (grant G0000934) and The Wellcome Trust (grant 068545/Z/02), and the UK Blood Services Collection of Common Controls (W. Ouwehand) funded by the Wellcome Trust. We also acknowledge the National Association for Colitis and Crohn's disease and the Wellcome Trust for supporting the case DNA collections, and support from UCB Pharma (unrestricted educational grant) and the NIHR Cambridge Biomedical Research Centre. The National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) IBD Genetics Consortium is funded by the following grants: DK62431 (S.R.B.), DK62422 (J.H.C.), DK62420 (R.H.D.), DK62432 and DK064869 (J.D.R.), DK62423 (M.S.S.), DK62413 (K.D.T.), NIH-AI06277 (R.J.X.) and DK62429 (J.H.C.). Additional support was provided by the Burroughs Wellcome Foundation (J.H.C.) and the Crohn's and Colitis Foundation of America (S.R.B., J.H.C.). We thank P. Gregersen and A. Lee (Feinstein Medical Research Institute) for their efforts and the use of control samples. This work was supported by grants from the DGTRE from the Walloon Region (n°315422 and CIBLES), the Communauté Française de Belgique (Biomod ARC), and the Belgian Science Policy organisation (SSTC Genefunc and Biomagnet PAI). E.L., S.Hansoul., D.F. and S.V. are fellows of the Belgian Fonds de la Recherche Scientifique (FNRS) and Fonds Wetenschappelijk Onderzoek-Vlaanderen (NFWO). C.S. is a fellow of the FRIA. We are grateful to all the clinicians, consultants and nursing staff who recruited subjects, including: J.-M. Maisin, V. Muls, J. Van Cauter, M. Van Gossum, P. Closset, P. Hayard and J.M. Ghilain (Erasme-BBIH-IBD); P. Mainguet, F. Mokaddem, F. Fontaine, J. Deflandre and H. Demolin (Ulg collaborators); J.-F. Colombel, M. Lemann, S. Almer, C. Tysk, Y. Finkel, M. Gassul, C. O'Morain, V. Binder and J.-P. Cézard (INSERM collaborators). Sincere thanks to L. Liang for his assistance in accessing the eQTL database, and to F. Merlin for expert technical assistance. Finally, we thank all individuals who contributed samples.

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Authors and Affiliations

1. Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
   Jeffrey C Barrett, Lon R Cardon & Carl A Anderson
2. Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Belgium
   Sarah Hansoul, Cécile Libioulle, Cynthia Sandor, Myriam Mni & Michel Georges
3. Department of Medicine, University of Chicago, 5801 South Ellis, Chicago, 60637, Illinois, USA
   Dan L Nicolae
4. Departments of Medicine and Genetics, Division of Gastroenterology, Yale University, Inflammatory Bowel Disease (IBD) Center, 300 Cedar Street, New Haven, 06519, Connecticut, USA
   Judy H Cho & Michael T Murtha
5. Department of Medicine, Division of Gastroenterology, University of Pittsburgh, School of Medicine, Hepatology and Nutrition, University of Pittsburgh Medical Center (UPMC) Presbyterian, 200 Lothrop Street, Pittsburgh, 15213, Pennsylvania, USA
   Richard H Duerr & Miguel D Regueiro
6. Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, 130 Desoto Street, Pittsburgh, 15261, Pennsylvania, USA
   Richard H Duerr & M Michael Barmada
7. Université de Montréal and the Montreal Heart Institute, Research Center, 5000 rue Belanger, Montreal, H1T 1C8, Quebec, Canada
   John D Rioux
8. The Broad Institute of Massachusetts Institute of Technology and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USA
   John D Rioux, Todd Green & Mark J Daly
9. Department of Medicine, Johns Hopkins University, Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, 1503 East Jefferson Street, Baltimore, 21231, Maryland, USA
   Steven R Brant, Themistocles Dassopoulos & Lisa Wu Datta
10. Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, 615 E. Wolfe Street, Baltimore, 21205, Maryland, USA
    Steven R Brant
11. Mount Sinai Hospital IBD Centre, University of Toronto, 441-600 University Avenue, Toronto, M5G 1X5, Ontario, Canada
    Mark S Silverberg & A Hillary Steinhart
12. Medical Genetics Institute and Inflammatory Bowel Disease (IBD) Center, Cedars-Sinai Medical Center, 8700 W. Beverly Blvd., Los Angeles, 90048, California, USA
    Kent D Taylor, Jerome I Rotter & Stephan R Targan
13. Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, H3A 1A1, Quebec, Canada
    Alain Bitton
14. The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada
    Anne M Griffiths
15. Department of Health Studies, University of Chicago, 5841 S. Maryland Avenue, Chicago, 60637, Illinois, USA
    Emily O Kistner & L Philip Schumm
16. Gastrointestinal Unit and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, 02114, Massachusetts, USA
    Ramnik J Xavier
17. Centre National de Génotypage, Evry, France
    Mark Lathrop, Ivo Gut, Simon Heath & Diana Zelenika
18. Department of Clinical Sciences, Unit of Hepatology and Gastroenterology, GIGA-R, Faculty of Medicine and CHU de Liège, University of Liège, Belgium
    Jacques Belaiche & Edouard Louis
19. Department of Gastroenterology, Clinique universitaire St Luc, UCL, Brussels, Belgium
    Olivier Dewit
20. Department of Hepatology and Gastroenterology, Ghent University Hospital, Belgium
    Debby Laukens & Martine de Vos
21. Department of Gastroenterology, University Hospital Leuven, Belgium
    Paul Rutgeerts & Severine Vermeire
22. Department of Gastroenterology, Erasmus Hospital, Free University of Brussels, Belgium
    André Van Gossum & Denis Franchimont
23. INSERM; Université Paris Diderot; Assistance Publique Hôpitaux de Paris; Hopital Robert Debré,
    Jean-Pierre Hugot
24. Université Paris Diderot, Paris, France
    Jean-Pierre Hugot
25. Division of Medical Sciences, Gastrointestinal Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK
    Hazel Drummond, Elaine Nimmo & Jack Satsangi
26. Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
    Tariq Ahmad
27. Department of Medical and Molecular Genetics, King's College London School of Medicine, 8th Floor Guy's Tower, Guy's Hospital, London, SE1 9RT, UK
    Natalie J Prescott, Clive M Onnie, Sheila A Fisher & Christopher G Mathew
28. Department of Statistics, University of Oxford, 1 South Parks Road, Oxford, OX1 3TG, UK
    Jonathan Marchini
29. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK
    Jilur Ghori, Suzannah Bumpstead, Rhian Gwilliam & Panos Deloukas
30. IBD research group, Addenbrooke's Hospital, University of Cambridge, CB2 2QQ, Cambridge, UK
    Mark Tremelling & Miles Parkes
31. Department of Gastroenterology and Hepatology, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK
    John Mansfield
32. Gastroenterology Unit, Radcliffe Infirmary, University of Oxford, Oxford, OX2 6HE, UK
    Derek Jewell
33. Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, 02114, Massachusetts, USA
    Mark J Daly

Authors

1. Jeffrey C Barrett
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2. Sarah Hansoul
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3. Dan L Nicolae
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4. Judy H Cho
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5. Richard H Duerr
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6. John D Rioux
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7. Steven R Brant
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8. Mark S Silverberg
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9. Kent D Taylor
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10. M Michael Barmada
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11. Alain Bitton
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12. Themistocles Dassopoulos
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13. Lisa Wu Datta
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14. Todd Green
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15. Anne M Griffiths
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16. Emily O Kistner
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17. Michael T Murtha
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18. Miguel D Regueiro
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19. Jerome I Rotter
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20. L Philip Schumm
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21. A Hillary Steinhart
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22. Stephan R Targan
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23. Ramnik J Xavier
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24. Cécile Libioulle
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25. Cynthia Sandor
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26. Mark Lathrop
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27. Jacques Belaiche
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28. Olivier Dewit
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29. Ivo Gut
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30. Simon Heath
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31. Debby Laukens
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32. Myriam Mni
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33. Paul Rutgeerts
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34. André Van Gossum
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35. Diana Zelenika
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36. Denis Franchimont
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37. Jean-Pierre Hugot
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38. Martine de Vos
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39. Severine Vermeire
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40. Edouard Louis
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41. Lon R Cardon
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42. Carl A Anderson
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43. Hazel Drummond
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44. Elaine Nimmo
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45. Tariq Ahmad
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46. Natalie J Prescott
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47. Clive M Onnie
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48. Sheila A Fisher
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49. Jonathan Marchini
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50. Jilur Ghori
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51. Suzannah Bumpstead
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52. Rhian Gwilliam
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53. Mark Tremelling
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54. Panos Deloukas
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55. John Mansfield
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56. Derek Jewell
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57. Jack Satsangi
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58. Christopher G Mathew
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59. Miles Parkes
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60. Michel Georges
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61. Mark J Daly
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Consortia

the NIDDK IBD Genetics Consortium

the Belgian-French IBD Consortium

the Wellcome Trust Case Control Consortium

Corresponding author

Correspondence toMark J Daly.

Additional information

This study is a joint effort of the Wellcome Trust Case Control Consortium, the NIDDK IBD Genetics Consortium and the French-Belgian IBD Consortium

This study is a joint effort of the Wellcome Trust Case Control Consortium, the NIDDK IBD Genetics Consortium and the French-Belgian IBD Consortium

This study is a joint effort of the Wellcome Trust Case Control Consortium, the NIDDK IBD Genetics Consortium and the French-Belgian IBD Consortium. A full list of authors is provided in the Supplementary Note

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Barrett, J., Hansoul, S., Nicolae, D. et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.Nat Genet 40, 955–962 (2008). https://doi.org/10.1038/ng.175

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• Received: 01 February 2008
• Accepted: 02 May 2008
• Published: 29 June 2008
• Issue Date: August 2008
• DOI: https://doi.org/10.1038/ng.175