We propose to extend the California Lupus Epidemiology Study (CLUES), which has established a racially/ethnically diverse cohort of over 400 individuals with systemic lupus erythematosus (SLE). The CLUES cohort builds on the successful California Lupus Surveillance Project, which established the incidence and prevalence of SLE in San Francisco County. Individuals identified through the surveillance effort were invited to participate in the longitudinal CLUES cohort. The study currently includes i) extensive clinical data, including physician-assessed measures of SLE disease activity, manifestations, and outcomes such as damage; ii) biologic data, including genetic, epigenetic, gene expression and environmental exposure information; and iii) data from structured interviews with participants covering sociodemographics, healthcare access and gaps, symptoms, disability, and a wide variety of patient-reported outcomes. This exceptionally broad and deep data collection has catalyzed a wide spectrum of SLE research studies, ranging from the examination of clinical and patient-reported outcomes in SLE to studies of DNA methylation across diverse racial/ethnic populations. Through data collection, analyses and dissemination, the overarching goal of CLUES is to advance our understanding of the natural history, treatment, outcomes and biology of SLE among diverse racial/ethnic and socioeconomic populations. In the renewal period, our aims are 1) lo continue longitudinal data collection on CLUES participants, including comprehensive patient-reported data, 2) to enhance and maintain a state-of-the-art biospecimen repository and provide access lo this resource to investigators, 3) to catalyze research on health disparities in vulnerable populations with SLE, including racial/ethnic minorities and those with low socioeconomic status, serving as a hub that brings together investigators and fosters high-impact, novel epidemiologic studies of the disease, and 4) to conduct two special projects, one examining the biology of SLE disease flares through investigations of epigenetic modifications during flares and after their resolution, and one examining the association of psychosocial stress with disease activity and flares. The overall project leverages outstanding institutional resources and builds on the proven track-record of the investigators in building a successful administrative and management infrastructure for CLUES, developing and maintaining longitudinal cohort studies, and creating effective systems for sharing clinical data and biospecimens. CLUES is unique because there are currently no population-based studies of Asians or Hispanic-Americans with SLE, two groups that are disproportionately affected by the disease and who comprise a significant and growing proportion of the U.S. population. In addition, the proposed special projects address disease flares, an area that is ripe for research and central lo advancing knowledge about the natural history, o...