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

OBJECTIVE: 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 predominantl y non-Jewish populations; in the three studies where Ashkenazi Jews were in cluded for analysis, the results have been widely divergent. Because Ashken azi 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 e xtended to the Ashkenazi population. In addition, we examined whether Ashke nazi Jewish patients with an early age of onset (less than or equal to 21 y r) showed greater evidence of linkage to this locus. METHODS: Linkage analysis for the IBD1 region was performed on 123 Ashkenaz i Jewish CD patients distributed among 53 families. Only patients with four Jewish grand parents were considered to be Jewish. Of the 123 Ashkenazi Je wish patients, 75 (61%) had an age of onset less than or equal to 21 yr. RESULTS: Ashkenazi Jews showed only modest evidence of linkage (nonparametr ic linkage 1.63, p = 0.05) to the IBD1 locus. However, when the Ashkenazi p opulation 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 o nset less than or equal to 21 yr (nonparametric linkage 3.02, p = 0.002). I n contrast, there was no evidence of linkage in the Jewish families where a ll affected individuals had an age of onset >21 yr. CONCLUSIONS: The IBD1 gene plays a greater role in conferring susceptibilit y to CD in Jews with early onset disease in Jews with late onset disease. ( Am J Gastroenterol 2001; 96:1127-1132. (C) 2001 by Am. Coll. of Gastroenter ology).