• Chromatin;
  • Genomics;
  • Heart failure;
  • Human studies;
  • Systems biology

Cardiovascular disease is a tremendous burden on human health and results from malfunction of various networks of biological molecules in the context of environmental stress. Despite strong evidence of heritability, many common forms of heart disease (heart failure in particular) have not yielded to genome-wide association studies to identify causative mutations acting via the disruption of individual molecules. Increasing evidence suggests, however, that genetic variation in noncoding regions is strongly linked to disease susceptibility. We hypothesize that epigenomic variation may engender different chromatin environments in the absence of (or in parallel with) changes in protein or mRNA sequence and abundance. In this manner, distinct—genetically encoded—chromatin environments can exhibit distinct responses to environmental stresses that cause heart failure, explaining a significant portion of the altered susceptibility that is observed in human disease.