The IBD1 locus for susceptibility to Crohn's disease has a greater impact in Ashkenazi Jews with early onset disease.

Abstract

Recent studies have suggested that a susceptibility gene located on chromosome 16 and designated IBD1 may contribute to the development of Crohn's disease (CD). However, these findings were observed in predominantly non-Jewish populations; in the three studies where Ashkenazi Jews were included for analysis, the results have been widely divergent. Because Ashkenazi Jews are known to have a higher incidence of the disease than non-Jews, we sought to determine whether this previously reported linkage could be extended to the Ashkenazi population. In addition, we examined whether Ashkenazi Jewish patients with an early age of onset (< or = 21 yr) showed greater evidence of linkage to this locus. Linkage analysis for the IBD1 region was performed on 123 Ashkenazi Jewish CD patients distributed among 53 families. Only patients with four Jewish grandparents were considered to be Jewish. Of the 123 Ashkenazi Jewish patients, 75 (61%) had an age of onset < or = 21 yr. Ashkenazi Jews showed only modest evidence of linkage (nonparametric linkage 1.63, p = 0.05) to the IBD1 locus. However, when the Ashkenazi population was subdivided on the basis of age of onset, there was a striking increase in linkage in families where affected individuals had an age of onset < or = 21 yr (nonparametric linkage 3.02, p = 0.002). In contrast, there was no evidence of linkage in the Jewish families where all affected individuals had an age of onset > 21 yr. The IBD1 gene plays a greater role in conferring susceptibility to CD in Jews with early onset disease than in Jews with late onset disease.