GENETIC EPIDEMIOLOGY OF SARCOIDOSIS IN AFRICAN AMERICANS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African-Americans. Candidate genes for the granulomatous inflammatory disorders Blau syndrome and Crohn's disease have been localized to the centrometric region of chromosome 16. We found no evidence of linkage in this general region, and could exclude from it a dominant gene with relative risk at least 5, or a recessive gene with relative risk at least 3, causing sarcoidosis. A multicenter study to perform a whole genome scan in the search for susceptibility genes has been completed, as has fine mapping of six candidate regions (1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13) with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We have conducted SNP typing on chromosome 5, confirming the presence of a susceptibility allele in this region. Further, using population structure we have isolated a unique set of families most likely to harbor the disease causing locus. Under new funding, we are currently conducting an admixture analysis to isolate genomic regions likely to harbor alleles of African origin in cases and compare to a set of unrelated controls to isolate sarcoidosis and sarcoidosis phenotype specific loci.