GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

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Funding from NIAMS RFA (AR-93-006) on Lupus in Women and Minorities made possible the collection of African-American pedigrees who were multiplex for systemic lupus erythematosus and the performance of a genome scan. In the first 31 pedigrees, we have found at least seven potential linkages which are relatively specific for lupus in African-Americans. Of these, the FcgammaRIIA locus provides the most consistent evidence for linkage with a lod score of 3.37 and a possibly significant affected sib-pair analysis (p=0.0005). The affected sib-pairs provide broad support for linkage from five of the surrounding loci spanning approximately 35 cM. D1s3462 also has suggestive evidence for linkage at lod=3.50. Five other loci obtain lod greater than 1.5 (D11s2002, D11s1392 and D3s1766) or p less than 0.01 by two applied allele sharing algorithms (D3s1053 and D17s2180) and have an effect which is predominately in the African-American pedigrees. Three additional loci appear to have effects found in families multiplex for lupus of both African and European origin (lod=2 to 2.5). We are resubmitting this proposal in order to obtain the resources with which to continue this work. Our specific aims for the coming funding period are: 1. To enlarge the collection of African-American pedigrees multiplex for lupus, 2. To convincingly establish linkage and pursue the identity of the genes responsible near FcgammaRIIA and D1s3462, 3. To establish the presence of other linkages with lupus in African-American pedigrees, 4. To evaluate other phenotype definitions by examining their relationship with the linkages established, and 5. To explore the criteria for lupus and the antinuclear antibody titer as quantitative trait phenotypes in these families. Results from this study are likely to contribute to understanding the genetics of systemic lupus erythematosus in African-Americans.