LINKAGE AND ASSOCIATION BETWEEN INFLAMMATORY BOWEL-DISEASE AND A LOCUS ON CHROMOSOME-12

Genetic epidemiological studies have shown that genetic factors are im portant in the pathogenesis of the idiopathic inflammatory bowel disea ses (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome s creen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses a t microsatellites surrounding D12S83 were performed in 122 North Ameri can Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. W e confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD score 2.76 [P =.00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD score 1.79 [P =.0021] bet cs een D12S 1724 and D12S90) and the group of UC-affected relative pairs (peak GEN EHUNTER-PLUS LOD score 1.82 [P =.0019] at D12S335). The TDT is positi ve at the D12S83 locus (global chi(2) = 16.41, 6 df, P = .012). In con clusion, we have independently confirmed linkage of IBD to the chromos ome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains a n IBD locus.