Not one but two inflammatory bowel disease susceptibility loci map to chromosome 16

The association of NOD2 gene mutations with inflammatory bowel disease (IBD) has been reported by multiple research groups. In this high-density linkage experiment using 39 microsatellite markers, Hampe et al. observed a triple-peaked configuration of the linkage curve with peak logarithm of odds (lod) scores of 2.7, 3.2, and 3.1 on proximal 16p, proximal 16q, and central 16q, respectively. An exploratory association analysis yielded a strong lead at D16S3068 (p = 0.00028 for all IBD, 0.0079 for Crohn's disease), and an IBD-associated haplotype consisting of three single nucleotide polymorphisms (p = 0.00027) was identified. After stratification for NOD2 genotype, the significance levels increased to p = 0.0001 for IBD phenotype; in subphenotype analysis, Crohn's disease and ulcerative colitis significances peaked at p = 0.002 and 0.0076, respectively. Hampe et al. not only confirm the importance of NOD2, but also provide a clear evidence of a second NOD2-independent IBD susceptibility locus on chromosome 16.