ABSTRACT Systemic sclerosis (SSc) and Systemic lupus erythematosus (SLE, or lupus) are autoimmune diseases with disproportionate prevalence and severity burdens among females of African ancestry (AA). Several environmental risk factors are suspected to play a role; however, relationships are complex and difficult to assess, thus much remains unknown. It is clear there is a critical need to improve studies of environmental exposure and autoimmune disease. In response, NIH has released a Notice of Special Interest entitled: “EXposome in Autoimmune Disease Collaborating Teams PLANning Awards (EXACT-PLAN)” intended to advance the study of the exposome in autoimmune diseases. This project is designed to contribute to this effort by establishing collaborations, study populations, and analytic approaches required to better characterize and assess holistic environmental exposures in health studies on autoimmune disease. We are well positioned to achieve this goal, as we leverage resources within the NIAMS-funded Improving Minority Health in Rheumatic Diseases (IMHRD) Core Center for Clinical Research at the Medical University of South Carolina (MUSC), which focuses on two autoimmune diseases, systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), will be leveraged. In addition, we present a strong research team with expertise in exposure science, epidemiology, human population genetics, social epigenomics, and clinical research necessary to improve exposome research on autoimmune disease. The overarching objective of this project is to improve understanding of how environmental exposures influence autoimmune disease. Goals are to develop resources needed to address the exposome within our study populations, develop innovative methodologies that will improve exposome studies, and to establish our research group as a major contributor to national research efforts centered on the exposome. The motivating hypothesis is that variability in environmental exposure (across the life course) is associated with worse autoimmune disease outcomes. The first specific aim focuses on establishing a cohort within the IMHRD study population that will support comprehensive characterization of the exposome. This also includes recruitment of 100 additional participants to enhance our existing study population specifically for exposome research. The second aim will develop novel data science tools to enhance integration and analysis of genetic, environmental, epigenetic, and social measures across the life course. Accomplishing these aims will establish a unique, health disparity cohort with autoimmune disease tailored specifically for exposome research, contribute findings that will improve understanding of complex links between the environment and autoimmune disease, and provide novel data science tools that will improve methodologies for analysis of the exposome.

PROJECT NARRATIVE Establishing an EXACT-PLAN cohort site within the NIAMS-funded Improving Minority Health in Rheumatic Diseases (IMHRD) Core Center for Clinical Research, will provide a unique, study population with existing autoimmune health disparities that will advance study of the exposome. Methods development will center on high-dimensional exposure settings, aiming to provide tools that will improve both the characterizations of and statistical analyses involving numerous co-exposures in exposome research.