Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (MethylationEPIC array)

African Americans (AA) are 70% more likely than Caucasian Americans (CA) to die from heart failure (HF) even after adjusting for known causes. Although the causal factors responsible for this racial disparity remain unknown, it is theorized that environmental stressors This alarming health disparity represents an important challenge to U.S. healthcare as global prevalence of heart failure has already exceeded epidemic levels with a disease burden that disproportionately impacts members of ethnic and racial minorities. The current multicohort study of cardiac DNA methylation identifies the cardiac epigenome as a previously unrecognized syntax that encodes race-based environmental differences in the failing human heart. The current study began as a pilot analysis of myocardial genome-wide DNA methylation via Illumina® HumanMethylation450 array with tandem RNA-sequencing analysis of 11 subjects with NYHA Stage IV heart failure. Unsupervised multidimensional scaling (MDS) of genome-wide cardiac DNA methylation identified patient race as the factor which accounted for the highest degree of methylation variability across the samples. The effects of race could not be explained by any other patient factors present in the electronic health record. This observation prompted a confirmatory analysis of 31 human HF biopsies using the Illumina Beadship MethylationEPIC array, wherein race-based separation was again seen as the principal determinant of patient heterogeneity via unsupervised deconvolution.