The Development of Epigenetics in the Study of Disease Pathogenesis

The study of epigenetics has its roots in the study of organism change over time and response to environmental change, although over the past several decades the definition has been formalized to include heritable alterations in gene expression that are not a result of alterations in underlying DNA sequence. In this chapter, we discuss first the history and milestones in the 100+ years of epigenetic study, including early discoveries of DNA methylation, histone posttranslational modification, and noncoding RNA. We then discuss how epigenetics has changed the way that we think of both health and disease, offering as examples studies examining the epigenetic contributions to aging, including the recent development of an epigenetic “clock”, and explore how antiaging therapies may work through epigenetic modifications. We then discuss a nonpathogenic role for epigenetics in the clinic: epigenetic biomarkers. We conclude by offering two examples of modern state-of-the-art integrated multi-omics studies of epigenetics in disease pathogenesis, one which sought to capture shared mechanisms among multiple diseases, and another which used epigenetic big data to better understand the pathogenesis of a single tissue from one disease.