AMERICAN FAMILIES WITH CROHNS-DISEASE HAVE STRONG EVIDENCE FOR LINKAGE TO CHROMOSOME-16 BUT NOT CHROMOSOME-12

Background & Aims: Two European genome-wide screens for inflammatory b ower disease have identified two significant regions of linkage on chr omosomes 16 (IBD1) and 12 (IBD2) and two regions with suggestive level s of significance (chromosomes 3p and 7q). The aim of this study was t o determine if there was evidence for linkage to these regions in non- Jewish and Ashkenazi Jewish families multiplex for Crohn's disease fro m the United States. Methods: One hundred forty-eight affected relativ e 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 eviden ce for replication of linkage was found only for the chromosome 16 loc us, IBD1, maximal at D16S769 (nonparametric linkage score [NPL], 2.49; P = 0.007). Analysis by ethnicity showed stronger evidence for Ashken azim (D16S769; NPL = 2.52; P = 0.007) than for non-Jewish white popula tions (D16S401; NPL = 1.40; P = 0.082). There was no significant evide nce for replication on chromosome 12 (IBD2). Minimal evidence for exte nsion of linkage evidence was observed for the chromosomes 3p and 7q r egions. Conclusions: American families, particularly Ashkenazim, have significant evidence for the Crohn's disease susceptibility locus, IBD 1, on chromosome 16, but not for IBD2 on chromosome 12.