GENETIC-ANALYSIS OF INFLAMMATORY BOWEL-DISEASE IN A LARGE EUROPEAN COHORT SUPPORTS LINKAGE TO CHROMOSOME-12 AND CHROMOSOME-16

Background & Aims: Inflammatory bower disease (IBD) is a complex disor der of unknown etiology, Epidemiological investigations suggest a gene tic basis for IBD. Recent genetic studies have identified several IBD linkages. The significance of these linkages will be determined by stu dies in large patient collections. The aim of this study was to replic ate IBD linkages on chromosomes 12 and 16 in a large European cohort. Methods: Three hundred fifty-nine affected sibling pairs from 274 kind reds were genotyped using microsatellite markers spanning chromosomes 12 and 16. Affection status of the sibling pairs was defined as Crohn' s disease (CD) or ulcerative colitis (UC). Results: Nonparametric stat istical analyses showed linkage for both chromosomes. Two-point result s for chromosome 12 peaked at D12S303 (logarithm of odds [LOD], 2.15; P = 0.003) for CD and at D12S75 (LOD, 0.92; P = 0.03) for UC. Multipoi nt analyses produced a peak LOD of 1.8 for CD. Chromosome 16 showed li nkage for CD at marker D16S415 (LOD, 1.52; P = 0.007). Multipoint supp ort peaked above markers D16S409 and D16S411 (LOD, 1.7). Conclusions: These data are consistent with linkage of IBD to chromosomes 12 and 16 . The replication of genetic risk loci in a large independent family c ollection indicates important and common susceptibility genes in these regions and will facilitate identification of genes involved in IBD.