1. ¹The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
2. ²Department of Medical & Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, London, UK
3. ³CSS – IRCCS Hospital, San Giovanni Rotondo, Italy
4. ⁴St Mark's Hospital, Harrow, UK
5. ⁵Department of Gastroenterology & Hepatology, University of Newcastle upon, Tyne, UK
6. ⁶Department of Gastroenterology, Guy's and St Thomas' Hospitals, London, UK
7. ⁷Montreal Jewish General Hospital, Montreal, Quebec, Canada
8. ⁸Centre Hospitalier de Sherbrooke, Sherbrooke, Quebec, Canada
9. ⁹Department of Gastroenterology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada

Correspondence: Dr JD Rioux, Broad Institute, One Kendall Sq., Bldg 300, Cambridge, MA 02139, USA. Tel: +1 617 252 1917; Fax: +1 617 252 1902; Prof. CG Mathew, Guy's King's and St Thomas' School of Medicine, 8th floor, Guy's Tower, Guy's Hospital, London SE1 9RT, UK

Received 19 October 2004; Revised 17 January 2005; Accepted 21 January 2005; Published online 20 April 2005.

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case–control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.