Nature Genetics, January 2009, Volume 41, Number 1
Common variants in the NLRP3 region contribute to Crohn's disease susceptibility
Alexandra-Chloe Villani, Mathieu Lemire, Genevieve Fortin, Edouard Louis, Mark S Silverberg, Catherine Collette, Nobuyasu Baba, Cecile Libioulle, Jacques Belaiche, Alain Bitton, Daniel Gaudet, Albert Cohen, Diane Langelier, Paul R Fortin, Joan E Wither, Marika Sarfati, Paul Rutgeerts, John D Rioux, Severine Vermeire, Thomas J Hudson & Denis FranchimontAbstract
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn’s disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn’s disease (Pcombined ¼ 3.49 109, odds ratio ¼ 1.78, confidence interval ¼ 1.47–2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies.