DNA graphic

Patrick Gaffney, MD


Oklahoma Medical Research Foundation

Genes and Human Disease


Epigenome profiling in human SLE

For many years, it has been recognized that people of African American race/ethnicity are at higher risk of developing systemic lupus than other racial/ethnic groups. African American patients with lupus are also more likely to have serious organ-specific forms of lupus such as lupus nephritis (lupus damaging the kidneys) and cutaneous lupus (damaging the skin). However, the reasons for the differences in risk are still unknown. This makes it especially important to understand the genetic risk factors for lupus in this population, and to develop treatments targeted to these risk factors. Dr. Gaffney’s study focuses on identifying the genetic risk factors of lupus in African Americans. Using samples taken from lupus patients and healthy African American donors, he will be able to determine which factors best predict lupus in this population. After completing this analysis, he aims to compare these genes to data from European Americans to determine which risk factors are unique to African Americans.


What this study means for people with lupus


This study will help uncover how race and ethnicity are linked to the development of lupus and to identify new treatment targets.

Systemic lupus erythematosus (SLE) is a challenging autoimmune disease characterized by a loss of immunologic tolerance to self-antigens and inflammatory processes that result in systemic end-organ damage. Substantial genetic and clinical differences exist between European American (EA) and African American (AA) SLE patients that result in disparities in the diagnosis, management and outcomes of SLE. Despite decades of research, our mechanistic understanding of SLE and the stark differences along racial lines remains elusive. Our lab’s focus has been to evaluate and understand how epigenetic regulation in specific cell types contributes to both disease- and race-specific SLE pathogenesis. We use a modified sciATAC-seq (single cell indexing assay for transposase-accessible chromatin) method to assess genome-wide disease- and race-specific regions of differential chromatin accessibility (dCA) in cell subtypes isolated from cryopreserved peripheral blood mononuclear cells (PBMCs). Integrating these data with genotyping data allows us to identify allelicly imbalanced variants that are associated with dCA (chromatin accessible QTLs or caQTLs), suggesting a mechanistic role for these variants in regulating CA. Our preliminary data collected from EA SLE cases and healthy controls demonstrate that 1) cryopreserved PBMCs are an excellent resource for defining dCA in multiple PBMC cell subtypes, 2) significant dCA exists between EA SLE case and control subjects, and 3) thousands of caQTLs are prevalent in multiple cell types, suggesting a mechanistic role for these variants in regulating CA. We now propose to evaluate disease-specific dCA and caQTL alterations in AA SLE, and then compare these data with our EA pilot data to identify race-specific alterations (AA vs EA). Integrating single-cell transcriptomic data and clinical data with the generated epigenetic data will allow for the generation of a mechanistic roadmap that connects genetic variation and dCA to deleterious transcriptomic, cellular and clinical phenotypes that underlie the disease-specific mechanisms of SLE and its remarkable race-specific disparities. Our goals for this proposal are to 1) define cell type-specific dCA that distinguishes disease-specific (AA SLE vs AA control) and race-specific (AA SLE from EA SLE) alterations in human SLE; 2) define how dCA and caQTLs shape the cell type-specific transcriptomic architectures in AA and EA SLE; and 3) identify clinical phenotypes associated with race-specific epigenomic alterations. We believe this project positions us at the leading edge to uncover pivotal new insights that will result in a better understanding of the important, but unexplored epigenome-based disease and race-dependent features of SLE.

Together, ManyOne Can make a difference!
Stay informed about events, research developments, and ways you can help. Sign up for updates