IBD Gene Mapping by Clinical and Population Subset

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PROJECT SUMMARY Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex genetic disorders of the gastrointestinal tract, and a major health burden to patients and society. Multicenter collaborative studies from 6 Genetics Research Centers (GRCs), organized with a Data Coordinating Center (DCC) to form the NIDDK IBD Genetics Consortium (IBDGC) has contributed to tremendous progress in dissecting IBD genetic etiology with identification of over 200 IBD loci by genome wide association studies (GWAS). Our GRC has contributed to all IBDGC studies and has taken roles in IBDGC leadership positions. Our particular GRC focus is uncovering and characterizing the genetic etiology of IBD, and variations in phenotypic expressivity and disease course, in the African-American population. We will continue to recruit and carefully phenotype African-American patients with IBD to maximize power for genetic and phenotype investigations. We will also recruit patients for parallel IBDGC focused studies in the Hispanic/LatinX population. We will expand and refine IBD loci contributing to the genetic risk of IBD in African-Americans by further GWAS, with sex-stratified, and fine-mapping approaches, and evaluate genotype-phenotype associations. We will perform a multiple immune disease association meta-analyses aggregating genome- wide data to maximize power to identify common immune mediated disease loci while also characterizing pleiotropy among the traits evaluated. We will provide critical resources in immune cells isolated from West- Africans and African-Americans and generate gene expression and epigenetic data for colocalization to better define disease causing variants and their effect on gene expression that result in the genetic risks of IBD in the African-American population. Lastly we will continue to participate in all IBDGC activities to maximize the impact of IBD genetics research by this cooperative funding mechanism.