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Editor,—Lesage and colleagues reported failure to detect linkage to the IBD2 locus on chromosome 12 in a panel of 95 families with two or more relatives affected by Crohn's disease, and offered some possible explanations (OpenUrlCrossRefPubMedWeb of Science). Linkage of inflammatory bowel disease (IBD) to this region was first detected in a panel of 160 families containing multiple cases of Crohn's disease, ulcerative colitis, or both.1 Lesage et aljustify the study of Crohn's disease families alone on the grounds that “genetic heterogeneity in susceptibility cannot be ruled out”, and they imply that studying the Crohn's disease subgroup of IBD should thus maximise their chance of successful replication. We concur entirely that genetic heterogeneity is important, and we have recently reported strong evidence that it does indeed apply to chromosome 12.2 However, our study of 367 multiply affected families suggested a significantly stronger contribution of this locus to ulcerative colitis than Crohn's disease.2 The difference between the linkage results for ulcerative colitis (LOD=3.91) and Crohn's disease (LOD=1.66) reached statistical significance in two separate tests for heterogeneity. In the light of these results, the validity of the exclusion map drawn by Lesage et al is undermined. The exclusion map was based on an assumed locus …
J P Hugot.hugot{at}cephb.fr