IL23R Arg381Gln is associated with childhood onset inflammatory bowel disease in Scotland

The discovery of NOD2/CARD15 as the first susceptibility gene in Crohn’s disease has contributed significantly to a fundamental change 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. Another study with major implications for the pathogenesis of Crohn’s disease as well as for investigation of all complex disorders has recently been published.3 The North American consortium performed an association study testing 308 332 markers spanning the entire genome in 567 patients with ileal Crohn’s disease 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 interleukin-23 receptor (IL23R) gene on chromosome 1p31. Replication was obtained in the index paper in a Jewish ancestry case-control analysis of patients with Crohn’s disease by transmission disequilibrium testing in 883 families with offspring affected by IBD and in a combined case-control analysis …