Identification of Susceptibility Genes for SLE of Amerindian Origin in Hispanics

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DESCRIPTION (provided by applicant): Item 6 Project Summary This application addresses broad Challenge Area (08) Genomics and Specific Challenge Topic, 08-AR-101 Genotyping Existing Cohorts in Rheumatic, Skin and Musculoskeletal Diseases. Systemic lupus erythematosus is not only primarily a disease of women, but it is also a disease affecting most severely women belonging to racial minorities. The reason for this is not clear, but there is evidence that it is two-fold: socio-economic and genetic. Indeed, studies have shown that patients of Hispanic ancestry develop SLE at a younger age, have a lower socio-economic status, have more organ involvement and more active disease combined with less social support and more abnormal illness-related behaviors. Further, Hispanic SLE patients have more abrupt onset of the disease and their social support is even lower than for African-American patients. Interestingly, studies have demonstrated that genetic factors, and in particular admixture, contribute more significantly to renal involvement in Hispanic patients than socio-economic factors, making the search for the identification of susceptibility genes of Amerindian origin in Hispanics an issue of urgency. We propose to perform a genome-wide association scan with large sets of cases and controls of Hispanic origin selected for the enrichment of two populations: European and Native American. Using whole-genome data, we will define the admixture through principal component analysis and the Amerindian contribution to the genetic risk for lupus. The best loci, within the framework of the funding will be selected for replication. This project will identify new loci for lupus of relevance in a minority population that suffers of a much more severe disease using cases and controls of enough statistical power and enriched for the appropriate Native American ancestry. All samples have, as for today, permission for immediate submission to dbGaP. Item 7. Project Narrative Lupus develops in women of Hispanic ancestry at a younger age, involves more organs, especially the kidneys. In our project, we will search for the identification of the genes associated with lupus in those of Amerindian origin in Hispanics. If we are lucky, then the advantages of Amerindian Hispanic ancestry will help us identify the exact changes in the DNA that help cause lupus.