PQG Seminar

Karen Conneely

Associate Professor, Department of Human Genetics
Emory University School of Medicine

Clonal hematopoiesis of indeterminate potential and DNA methylation in human aging

Age-related changes to the epigenome are well-documented, especially the pattern of genome-wide DNA methylation (DNAm) changes observed in blood and other tissues. This pattern is so robust it can accurately estimate individual age and predict lifespan and health outcomes, but its underlying causes remain to be elucidated. Age is also associated with an increased prevalence of somatic mutation in nuclear DNA, particularly in frequently regenerating cells such as hematopoietic stem cells (HSCs). Occasionally, mutations in HSCs may occur in a leukemogenic driver gene causing clonal selection and expansion – termed clonal hematopoiesis of indeterminate potential (CHIP). The genes most commonly implicated in CHIP, DNMT3A and TET2, have roles in epigenomic regulation. Thus, we hypothesized that age-related DNAm changes may be partially driven by age-related CHIP. Here, I will review work on DNAm and aging by our group and others, followed by recent work on CHIP and aging. I will then describe the results from an epigenome-wide association study (EWAS) to test for association between CHIP and DNAm in two population-based cohort studies.