Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with adverse cardiometabolic
health across the lifespan. Due to their widespread use in consumer and industrial products, the developing
fetus, infant, and child may be exposed via transplacental transfer, breast milk, dust ingestion, diet, and drinking
water. The long biological half-lives of some PFAS, which can range from 2-7 years in humans, intensifies
concerns about the risk of continued exposure and associated health effects. While elevated exposure to PFAS
in utero and during childhood may predispose exposed children to increased adiposity, systolic blood pressure,
and cholesterol levels, the biological mechanisms underlying the PFAS-cardiometabolic risk associations are not
well-understood. Growing evidence suggests that one mechanism by which PFAS may contribute to
cardiometabolic risk is through changes in DNA methylation (DNAm). As such, DNAm-derived epigenetic clocks
have emerged as a promising biomarker of aging and disease. Recent studies suggest gestational and childhood
exposure to environmental pollutants including phthalates, indoor air pollutants, and smoking influence the rate
of epigenetic aging. However, the link between PFAS, epigenetic aging, and cardiometabolic health in children
remains unknown. We will leverage data from the HOME Study, a prospective cohort of pregnant women and
their children from Cincinnati, OH, to calculate novel epigenetic biomarkers of aging and disease. The HOME
Study has repeated measures of serum PFAS concentrations across childhood, comprehensive assessments of
cardiometabolic markers in early adolescence, and DNA methylation at birth and 12 years of age. This will allow
us to: 1) determine if gestational and childhood PFAS are associated with epigenetic age acceleration (EGAA)
at birth and epigenetic age acceleration (EAA) in early adolescence; 2) determine if EGAA and EAA are
associated with increased cardiometabolic risk in early adolescence using multiple markers of cardiometabolic
health; and 3) explore the mediating role of EGAA in the association between gestational PFAS exposure and
cardiometabolic risk in early adolescence. By using these novel epigenetic clocks and quantifying the persistence
of these effects into adolescence, we will gain valuable insights into the impact of PFAS toxicity on biological
processes that may affect early life development and subsequent PFAS-associated cardiometabolic risk. This
diversity supplement will train a promising graduate student to enhance her training in environmental
epidemiology and biostatistical methods, and learn how to estimate and interpret biological aging measures
derived from high dimensional DNA methylation data.
