The discovery of NOD2/CARD15 as the first susceptibility gene in Crohn's disease (CD) has greatly contributed to a fundamental alteration in the direction of basic research in Inflammatory Bowel Disease (IBD), triggering renewed interest in the integrity of the innate immune response in IBD and appropriate orchestration of a subsequent adaptive immune response.(1;2) More widely, in all complex diseases this finding in 2001 provided a much-welcomed and needed proof of principle for non-parametric linkage analysis.
Recently, another study with major implications both for CD pathogenesis as well as for investigation of all complex disorders has been published in Science.(3) The North-American consortium performed an association study testing 308,332 markers spanning the entire genome in 567 ileal CD patients and 571 controls of non-Jewish European ancestry. Of the three markers reported to retain significance after stringent Bonferroni correction, two were located in the NOD2/CARD15 gene. The third marker (rs11209026) was a non-synonymous variant in the IL23R (interleukin-23 receptor) gene on Chromosome 1p31. Replication was obtained in the index paper in a Jewish-ancestry ileal CD case-control analysis, by transmission disequilibrium testing (TDT) in 883 families with IBD affected offspring and in a combined case-control analysis of these three cohorts (IBD, p=6.62E-19).
- genome-wide association study
- inflammatory bowel disease