The epigenome orchestrates the flow of information for genotype to phenotype by modifying the activity of non-protein-coding regulatory elements in specific cell types and under different environmental conditions. In the post-GWAS era, significant efforts have been dedicated to understanding how disease-associated non-protein-coding risk alleles influence the flow of genetic information in specific cell types by modifying the epigenetic marks on specific histones. In this way, risk alleles can induce epigenetic “footprints” that show up as allele-specific changes in the magnitude of a specific histone modification. In 2018, Dr. Gaffney’s team developed an innovative epigenome-guided approach that captures distinct cell type, cell state, and allele-specific epigenetic profiles and maps them in the context of the three-dimensional genome to gain new insights into the potential molecular mechanism of risk alleles (Pelikan, et al. Nature Comm 2018).
They are now leveraging this approach in combination with single-cell sequencing technologies to map SLE-specific epigenetic footprints in different immune cell types. Further, they are using this approach to determine if sex and race-specific disparities in the clinical manifestations of SLE result, in part, from differences in these epigenetic footprints.