Nature Genetics, AUGUST 2008, VOLUME 40, NUMBER 8

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

Jeffrey C Barrett, Sarah Hansoul, Dan L Nicolae, Judy H Cho, Richard H Duerr, John D Rioux, Steven R Brant, Mark S Silverberg, Kent D Taylor, M Michael Barmada, Alain Bitton, Themistocles Dassopoulos, Lisa Wu Datta, Todd Green, Anne M Griffiths, Emily O Kistner, Michael T Murtha, Miguel D Regueiro, Jerome I Rotter, L Philip Schumm, A Hillary Steinhart, Stephan R Targan, Ramnik J Xavier, the NIDDK IBD Genetics Consortium, Cecile Libioulle, Cynthia Sandor, Mark Lathrop, Jacques Belaiche, Olivier Dewit, Ivo Gut, Simon Heath, Debby Laukens, Myriam Mni, Paul Rutgeerts, Andre Van Gossum, Diana Zelenika, Denis Franchimont, Jean-Pierre Hugot, Martine de Vos, Severine Vermeire, Edouard Louis, the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Lon R Cardon, Carl A Anderson, Hazel Drummond, Elaine Nimmo, Tariq Ahmad, Natalie J Prescott, Clive M Onnie, Sheila A Fisher, Jonathan Marchini, Jilur Ghori, Suzannah Bumpstead, Rhian Gwilliam, Mark Tremelling, Panos Deloukas, John Mansfield, Derek Jewell, Jack Satsangi, Christopher G Mathew, Miles Parkes, Michel Georges & Mark J Daly

Abstract

Several risk factors for Crohn’s disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn’s disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls.

The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.