Genetics of inflammatory bowel disease

: Genetic influence in the susceptibility to inflammatory bowel disease (IBD) is suggested by racial, ethnic, and familial aggregation of disease. Increased concordance for IBD in monozygotic compared with dizygotic twins suggests that genetic rather than environmental factors are primarily responsible for the familial aggregation. A dramatically increased risk for IBD in siblings compared with spouses of affected individuals and many instances of temporal and geographic separation of disease onset in affected relatives also suggest that the familial aggregation of IBD is primarily due to genetic factors. The complex genetics of IBD involves incomplete penetrance and probably involves oligogenic inheritance and genetic heterogeneity. Identification of subclinical markers and markers of genetic heterogeneity in IBD to address the likely problems of incomplete penetrance and genetic heterogeneity would greatly simplify the task of finding IBD susceptibility loci in well-designed genetic marker association and linkage studies. Potential subclinical markers and markers of genetic heterogeneity in IBD are reviewed, as are candidate-gene studies. In addition to candidate-gene studies, future studies should include whole genome screening by using polymorphic genetic markers throughout the genome systematically to map IBD-susceptibility loci. Currently available molecular biologic technology with highly informative polymorphic genetic markers should permit successful identification of IBD-susceptibility genes.