American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12

Background & Aims: Two European genome-wide screens for inflammatory bower disease have identified two significant regions of linkage on chromosomes 16 (IBD1) and 12 (IBD2) and two regions with suggestive levels of significance (chromosomes 3p and 7q). The aim of this study was to determine if there was evidence for linkage to these regions in non-Jewish and Ashkenazi Jewish families multiplex for Crohn's disease from the United States. Methods: One hundred forty-eight affected relative pairs, 34% Ashkenazim, were genotyped with 10-14 highly polymorphic markers overlying each candidate region. Nonparametric multipoint and two-point linkage analyses were performed. Results: Significant evidence for replication of linkage was found only for the chromosome 16 locus, IBD1, maximal at D16S769 (nonparametric linkage score [NPL], 2.49; P = 0.007). Analysis by ethnicity showed stronger evidence for Ashkenazim (D16S769; NPL = 2.52; P = 0.007) than for non-Jewish white populations (D16S401; NPL = 1.40; P = 0.082). There was no significant evidence for replication on chromosome 12 (IBD2). Minimal evidence for extension of linkage evidence was observed for the chromosomes 3p and 7q regions. Conclusions: American families, particularly Ashkenazim, have significant evidence for the Crohn's disease susceptibility locus, IBD1, on chromosome 16, but not for IBD2 on chromosome 12.