IBD Gene Mapping by Clinical and Population Subsets

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DESCRIPTION (provided by applicant): Genetic heterogeneity has been a major obstacle for identifying genes for the complex genetic disorder, inflammatory bowel disease. We have demonstrated that stratified analysis by age at onset and severity can markedly reduce genetic heterogeneity for the IBD1 locus. Further stratified analysis based on clinical and epidemiological covariates may have great power to identify and narrow loci. Despite the large African American population with IBD in North America, no genetic studies have included African Americans, perhaps in part to reduce problems of genetic heterogeneity and inadequate sample availability. African ancestral populations however may have greater power to reduce problems of extensive linkage disequilibrium that has plagued narrowing the IBD 3 and 1BD5 loci. We have developed two proposals that take advantage of the large number of IBD patients to be made available for Genetic Research Centers of the proposed NIH lBD Genetics Research Consortium: (A) Sub-analyses, of present and future genome wide and locus specific linkage data, as based on defined clinical and epidemiological characteristics to identify, confirm and/or refine IBD loci. (B) Recruitment, phenotypic characterization and genotyping of African American IBD patients for locus specific linkage disequilibrium studies in the three loci where linkage disequilibrium has already been identified, IBD1, IBD3 and IBD5. We will perform one of these proposals as directed by the consortium steering committee and in collaboration with other consortium investigators.