R01MD015395

Social Factors, Epigenomics, and Lupus in African American Women (SELA) - Abstract

Systemic Lupus Erythematosus (SLE, or Lupus) is a prototypic autoimmune disease marked by a disproportionate prevalence and severity burden in women of African ancestry (AA). There is a critical need for efforts that identify the molecular mechanisms through which positive and negative social determinants of health contribute to the Lupus health disparity, so that progress in improving disease outcomes can be made and the health disparities gap can be closed.

This research project addresses the objectives of PAR-19-372 to "1) advance understanding of mechanisms by which social factors lead to epigenetic changes that affect minority health and health disparities, and 2) promote epigenetics research to better predict disease or resiliency among health disparity populations." We are seeking to identify and characterize the epigenetic mechanisms by which positive and negative social experiences affect gene function and thereby influence SLE in AA women.

We have previously shown that racial discrimination is associated with worse disease outcomes in AA women, while social support seems to have a positive impact. Multiple environmental exposures, including psychosocial factors, affect variation in DNA methylation. Despite their influence on SLE in AA women, it is not known how environmental experiences affect and operate through the individual epigenome to influence disease.

We will test the following hypotheses in AA women: 1) exposure to adverse and protective social contexts is associated with epigenomic changes involving immune, inflammatory, and energy metabolism pathways, which in turn are associated with disease outcomes; and 2) social support compensates for the detrimental, independent effect of racial discrimination on SLE through epigenetic and gene regulatory mechanisms.

We will leverage our existing registry and infrastructure, together with our community partnership, to accomplish this community-engaged integrative mechanistic study. We will enroll 300 AA women with SLE and 300 unaffected AA women, collect sociodemographic, medical, genotypic, leukocyte proportion, DNA methylation, and gene expression data, and use validated measures to assess life course racial discrimination and social support.

We propose to: identify variation in DNA methylation (DNAm) associated with (a) exposure to racial discrimination, (b) exposure to social support, and (c) epigenetic age acceleration (Aim 1); assess whether social DNAm sites affect gene expression (Aim 2); and identify the synergistic effects of social factors on DNAm changes on SLE and develop a social factors-DNAm predictive model for disease outcomes (Aim 3).

This will be the first study investigating epigenetic mechanisms by which risk and resiliency factors affect gene function and Lupus in AA women. These results will greatly expand the knowledge of how social factors affect gene function, disease outcomes, and health disparities, which might inform the development of effective interventions to close the health disparities gap. Finally, given the shared etiologic mechanisms, these findings have broader applicability to other autoimmune diseases.

The Medical University Of South Carolina

TO SUPPORT BASIC, CLINICAL, SOCIAL, AND BEHAVIORAL RESEARCH, PROMOTE RESEARCH INFRASTRUCTURE AND TRAINING, FOSTER EMERGING PROGRAMS, DISSEMINATE INFORMATION, AND REACH OUT TO MINORITY AND OTHER HEALTH DISPARITY COMMUNITIES. THE NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES (NIMHD) HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS: (1) THE CENTERS OF EXCELLENCE PROGRAM PROMOTES RESEARCH TO IMPROVE MINORITY HEALTH AND/OR REDUCE AND ELIMINATE HEALTH DISPARITIES, BUILDS RESEARCH CAPACITY FOR MINORITY HEALTH AND HEALTH DISPARITIES RESEARCH IN ACADEMIC INSTITUTIONS, ENCOURAGES PARTICIPATION OF HEALTH DISPARITY GROUPS AND COMMUNITIES IN BIOMEDICAL AND BEHAVIORAL RESEARCH AND PREVENTION AND INTERVENTION ACTIVITIES, AND BRINGS TOGETHER INVESTIGATORS FROM RELEVANT DISCIPLINES IN A MANNER THAT WILL ENHANCE AND EXTEND THE EFFECTIVENESS OF THEIR RESEARCH, (2) NIMHD RESEARCH ENDOWMENT PROGRAM BUILDS RESEARCH CAPACITY AND INFRASTRUCTURE AT ELIGIBLE NIMHD CENTERS OF EXCELLENCE OR ELIGIBLE SECTION 736 HEALTH PROFESSIONS SCHOOLS (42 U.S.C. 293) TO FACILITATE MINORITY HEALTH AND OTHER HEALTH DISPARITIES RESEARCH TO CLOSE THE DISPARITY GAP IN THE BURDEN OF ILLNESS AND DEATH EXPERIENCED BY RACIAL AND ETHNIC MINORITY AMERICANS AND OTHER HEALTH DISPARITY POPULATIONS, PROMOTES A DIVERSE AND STRONG SCIENTIFIC, TECHNOLOGICAL AND ENGINEERING WORKFORCE, AND EMPHASIZES THE RECRUITMENT AND RETENTION OF UNDERREPRESENTED MINORITIES AND OTHER SOCIO-ECONOMICALLY DISADVANTAGED POPULATIONS IN THE FIELDS OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND OTHER AREAS OF THE SCIENTIFIC WORKFORCE, (3) THE CENTERS OF EXCELLENCE ON ENVIRONMENTAL HEALTH DISPARITIES RESEARCH TO STIMULATE BASIC AND APPLIED RESEARCH ON ENVIRONMENTAL HEALTH DISPARITIES, (4) MINORITY HEALTH AND HEALTH DISPARITIES INTERNATIONAL RESEARCH TRAINING PROGRAM (MHIRT) AWARDS ENABLE U.S. INSTITUTIONS TO TAILOR SHORT-TERM BASIC SCIENCE, BIOMEDICAL AND BEHAVIORAL MENTORED STUDENT INTERNATIONAL RESEARCH TRAINING OPPORTUNITIES TO ADDRESS GLOBAL ISSUES RELATED TO UNDERSTANDING, REDUCING, AND ELIMINATING HEALTH DISPARITIES, (5) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, ENCOURAGES SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (6) SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTERS TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) HEALTH DISPARITIES RESEARCH PROJECT GRANTS (RPG) SUPPORT INNOVATIVE PROJECTS TO ENHANCE OUR UNDERSTANDING OF BIOLOGICAL MECHANISMS, SOCIAL, BEHAVIORAL, AND HEALTH SERVICES THAT CAN DIRECTLY AND DEMONSTRABLY CONTRIBUTE TO THE IMPROVEMENT IN MINORITY HEALTH AND THE ELIMINATION OF HEALTH DISPARITIES WHICH INCLUDES THE (8) RESEARCH CENTERS IN MINORITY INSTITUTIONS (RCMI) BUILD CAPACITY FOR BASIC BIOMEDICAL AND/OR BEHAVIORAL RESEARCH, CLINICAL AND TRANSLATIONAL RESEARCH (RCTR) AND A NETWORK (RCTN) BY FOCUSING ON INSTITUTIONAL RESOURCE DEVELOPMENT, SUCH AS SUPPORTING CORE RESEARCH FACILITIES AND STAFF, PURCHASING ADVANCED INSTRUMENTATION, AND LABORATORY RENOVATIONS/ALTERATIONS (9) CLINICAL RESEARCH EDUCATION AND CAREER DEVELOPMENT (CRECD) AWARDS PROVIDE DIDACTIC TRAINING AND MENTORED CLINICAL RESEARCH EXPERIENCES TO DEVELOP INDEPENDENT RESEARCHERS WHO CAN LEAD CLINICAL RESEARCH STUDIES, ESPECIALLY THOSE ADDRESSING HEALTH DISPARITIES, (10) PATHWAY TO INDEPENDENCE AWARDS (K99/R00) TO INCREASE AND MAINTAIN A STRONG COHORT OF NEW AND TALENTED, NIH-SUPPORTED, INDEPENDENT INVESTIGATORS. (11) NIH RESEARCH CONFERENCE GRANT AND NIH RESEARCH CONFERENCE COOPERATIVE AGREEMENT PROGRAMS SUPPORT HIGH-QUALITY CONFERENCES THAT ARE RELEVANT TO THE MINORITY HEALTH AND HEALTH DISPARITIES, (12) TRANSDISCIPLINARY COLLABORATIVE CENTERS FOR HEALTH DISPARITIES RESEARCH COMPRISE REGIONAL COALITIONS OF ACADEMIC INSTITUTIONS, COMMUNITY ORGANIZATIONS, SERVICE PROVIDERS AND SYSTEMS, GOVERNMENT AGENCIES AND OTHER STAKEHOLDERS CONDUCTING COORDINATED RESEARCH, IMPLEMENTATION AND DISSEMINATION ACTIVITIES THAT TRANSCEND CUSTOMARY APPROACHES AND SILO ORGANIZATIONAL STRUCTURES TO ADDRESS CRITICAL QUESTIONS AT MULTIPLE LEVELS IN INNOVATIVE WAYS FOCUSED ON PRIORITY RESEARCH AREAS IN MINORITY HEALTH AND HEALTH DISPARITIES, (13) RUTH L. KIRSCHSTEIN NRSA INDIVIDUAL PREDOCTORAL FELLOWSHIP

93.310 - Trans-NIH Research Support

National Institute for Minority Health and Health Disparities (NIMHD) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Charleston, South Carolina 29425 United States

Single Zip Code

Social Epigenomics Research Focused on Minority Health and Health Disparities (R01-Clinical Trial Not Allowed) (PAR-19-372)

Amendment Since initial award the End Date has been shortened from 04/30/26 to 09/24/24 and the total obligations have increased 347% from $669,569 to $2,991,296.