The IBD2 locus shows linkage heterogeneity between ulcerative colitis and Crohn disease

The IBD2 locus on chromosome 12 has been linked to both Crohn disease (CD) and ulcerative colitis (UC) but has not been detected in some CD-dominated data sets. In the present study, we genotyped 581 relative pairs with inflammatory bowel disease (252 from CD-only families, 138 from UC-only families, and 191 from mixed families containing cases of both CD and UC), using 12 markers spanning the IBD2 locus. A GENEHUNTER-PLUS multipoint LOD score of 3.91 was detected for pairs from UC-only families, compared with 1.66 for CD-only and 1.29 for mixed families. The difference between the LOD scores for UC and CD was significant in two different tests for heterogeneity (P=.0057 for one test and P=.0375 for the other). IBD2 thus appears to make a major contribution to UC susceptibility but to have only a relatively minor effect with regard to CD, for which there may be substantially more locus heterogeneity.