Author Interviews, Genetic Research, Heart Disease, JAMA / 06.04.2018
Epigenetic DNA Variants Predictive of Coronary Artery Disease
MedicalResearch.com Interview with:
Stella Aslibekyan, PhD
Associate Professor
PhD Program Director
Department of Epidemiology
University of Alabama at Birmingham
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics-- the study of mitotically heritable changes in gene expression-- has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels.
In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment.
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