Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease that has the potential tocause serious morbidity and early mortality and is responsible for tremendous costs to affected individualsand society. A striking feature of SLE is variation in health outcomes. In particular, substantial researchdocuments ethnic disparities in SLE risk and severity. In spite of the magnitude of variation in SLE healthoutcomes, and the potential importance for patients, physicians and society, many questions remain aboutthe underlying causes. For example, it remains unclear whether ethnic disparities in SLE outcomes reflectprimarily individual, social, environmental or genetic variation in risk or interactions among these factors.Our lack of understanding is at least partially due to the challenges of assembling a sufficiently large anddiverse cohort of SLE patients, measuring the full range of potentially important risk factors, and accuratelyassessing health outcomes. The current proposal represents a unique combination of clinical andinvestigative resources that has been developed to address this critically important issue. Specifically, wewill: 1) determine the relative contributions of demographic, socioeconomic, psychosocial, behavioral andgenetic factors to health outcomes in SLE; and 2) characterize changes in health outcomes over time andthe contribution of these explanatory factors to temporal changes in outcome. A primary focus of this projectwill be the relationship of ethnicity to SLE outcomes, and in particular understanding the roles of geneticsand other factors (e.g., socioeconomic, psychosocial, etc.) as mediators of ethnic disparities in outcome.Our study population will be approximately 1,000 SLE patients enrolled in the Lupus Outcome Study. Wewill use validated instruments to assess the following outcomes: general health status, disease activity andcumulative damage. A unique feature of the current proposal is the depth and breadth of potentiallyimportant explanatory factors that will be considered. In addition to traditional risk factors, these includenovel measures of community characteristics obtained through 'geocoding' to small geographic areas andancestry informative genetic markers. Due to the size and scope of this project, in conjunction with the richresources and expertise of the MCRC, this project should substantially increase our understanding of healthdisparities in SLE and their underlying causes and guide efforts to remedy these disparities.
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