Social Factors, Epigenomics and Lupus Assessment (SELA)

Emory University, Atlanta GA

Investigators

Linked publications, trials & patents

Abstract

Modified Project Summary/Abstract Section Systemic lupus erythematosus (SLE, or lupus) is a prototypic autoimmune disease marked by a disproportionate variation in prevalence and severity burden among demographic groups. There is a critical need for efforts that identify the molecular mechanisms through which positive and negative individual and societal experiences contribute to lupus outcomes, so that progress in improving disease outcomes can be made. This research project addresses the objectives of PAR-19-372 to “1) advance understanding of mechanisms by which societal factors lead to epigenetic changes that affect health, and 2) promote epigenetics research to better predict disease or resiliency.” We are seeking to identify and characterize the epigenetic mechanisms by which positive and negative societal experiences affect gene function and thereby influence SLE. We and others have previously shown that societal factors affect SLE outcomes. Multiple genetic and societal factors affect variation in DNA methylation. Despite their influence on SLE, it is not known how individual and societal experiences affect and operate through the individual epigenome to influence disease. We will test the hypothesis that exposure to adverse and protective societal contexts is associated with epigenomic changes involving immune, inflammatory, and energy metabolism pathways, which in turn are associated with disease outcomes. We will leverage our existing registry and infrastructure, together with our public partnership, to enroll 300 patients with SLE and 300 matched controls, collect demographic, medical, genotypic, leukocyte proportion, DNA methylation, and gene expression data, and use validated measures to assess multiple domains of societal support. We propose to: identify variation in DNA methylation (DNAm) associated with (a) exposure to domains of societal support, and (b) epigenetic age acceleration (Aim 1); to assess whether these DNAm sites affect gene expression (Aim 2); and identify the synergistic effects of societal factors on DNAm changes on SLE and develop a societal factors-DNAm predictive model for disease outcomes (Aim 3). This will be the first study investigating epigenetic mechanisms by which societal experiences affect gene function and lupus. These results will greatly expand the knowledge of how societal factors affect gene function and disease outcomes, which might inform the development of effective interventions to eradicate SLE. Finally, given the shared etiologic mechanisms, these findings have broader applicability to other autoimmune diseases.