A genomewide analysis provides evidence for novel linkages in inflammatorybowel disease in a large European cohort

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing in testinal inflammation, typically starting in early adulthood. IBD is subdiv ided into two subtypes, on the basis of clinical and histologic features: C rohn disease and ulcerative colitis (UC). Previous genomewide searches iden tified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we perfor med a 9-cM genomewide search for susceptibility loci in 268 families contai ning 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectiv ely. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turne r syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort , has confirmed three previous IBD linkages and has provided evidence for f ive additional regions that may harbor IBD predisposition genes.