Exclusion of linkage of Crohn's disease to previously reported regions on chromosomes 12, 7, and 3 in the Belgian population indicates genetic heterogeneity

Susceptibility to inflammatory bowel disease (IBD) is significantly determi ned by genetic factors. Linkage data from genome-wide searches have identif ied regions on chromosomes 16, 12, 7, and 3. Our goal was to replicate thes e four regions in a Belgian population of IBD families. Fifty-four IBD fami lies were studied (47 with Crohn' a disease [CD] and 7 with mixed CD and ul cerative colitis, containing 79 affected sibpairs (68 CD only, 11 mixed) fo r the regions previously implicated to chromosomes 16, 12, 7, and 3. In thi s study, no evidence for linkage was found on any of the four chromosomal r egions studied for either the whole IBD dataset or the CD subgroup. The mul tipoint maximum logarithm of odds scores were less than 0.7 for all four re gions. Exclusion mapping could significantly exclude chromosomes 3, 7, and 12. Despite earlier findings, we could significantly exclude linkage of CD with previously reported regions on chromosomes 12, 7, and 3, and could not find evidence for linkage to chromosome 16. It is important to report thes e findings in light of the genetic heterogeneity of IBD. A genome-wide sear ch on a larger group of affected siblings is being analyzed to detect other possible susceptibility loci in the Belgian population.