The Social Factors, Epigenomics, and Lupus in African American Women (SELA) study: protocol for an observational mechanistic study examining the interplay of multiple individual and social factors on lupus outcomes in a health disparity population

Abstract

AbstractIntroductionDespite the disproportional impact of systemic lupus erythematosus (SLE) on historically marginalized racial and ethnic communities, the individual and sociocultural factors underlying these health disparities remain elusive. We report the design and methods for a study aimed at identifying the epigenetic mechanisms by which risk and resiliency social factors affect gene function and thereby influence SLE in a health disparity population.Methods and analysisThe Social Factors, Epigenomics, and Lupus in African American Women (SELA) study is a cross-sectional, case-control study involving the Medical University of South Carolina, Emory University, and Wake Forest School of Medicine. A total of 600 self-reported African American females will be invited to participate. All participants will respond to questionnaires that capture detailed sociodemographic and medical history, validated measures of racial discrimination, vicarious racism stress, social support, healthcare utilization and lost productivity, as well as disease activity and damage for cases. Physician-reported disease activity will also be incorporated Participants will choose if they wish to receive their genetic ancestry estimates and be involved in research. Blood samples are required to provide serum, plasma, PBMCs counts, DNA and RNA. The primary goals of SELA are to identify variation in DNA methylation (DNAm) associated with self-reported exposure to racial discrimination and exposure to social support, to evaluate whether social DNAm sites affect gene expression, to identify the synergistic effects of social factors on DNAm changes on SLE, and to develop a social factors-DNAm predictive model for disease outcomes. This study was approved by and will be conducted in cooperation with the Sea Island Families Project Citizen Advisory Committee.Discussion and disseminationSELA will respond to the pressing need to identify the regulatory mechanisms through which social exposures influence SLE in a health disparity population, clarify the interplay and underlying mechanism by which various positive and negative social determinants of health influence epigenomic variation, and how the resulting biological changes may contribute to the lupus health disparity. Results will be published and shared with patients and the community. These findings may inform the development of psychosocial interventions that prevent or mitigate risk exposures, and services or interventions that promote positive exposures. Development of these novel treatments and preventative interventions, as informed by the results of this study, is paramount to the closure of the health disparities gap.