Lifetime Postnatal Exposure to Perfluoroalkyl Substance Mixture and DNA Methylation at Twelve Years of Age

Per- and polyfluoroalkyl substance (PFAS) exposure has been linked to DNA methylation changes in neonates and adults. We previously reported that prenatal PFAS exposure may have a durable impact on DNA methylation from birth to adolescence. However, few studies have examined the association of postnatal PFAS exposure with alterations in DNA methylation. We examined the associations of lifetime postnatal PFAS mixture exposure with leukocyte DNA methylation in 154 adolescents from the HOME Study (2003-2006; Cincinnati, Ohio). Lifetime postnatal PFAS mixture exposure was estimated using latent profile analysis of four PFAS concentrations measured at birth, and ages 3, 8, and 12 years. We measured DNA methylation in peripheral leukocytes at 12 years using the Illumina HumanMethylation EPIC BeadChip. We estimated covariate-adjusted associations between postnatal PFAS mixture concentrations and DNA methylation measures using linear regression and used KEGG enrichment analysis to identify molecular pathways. Four significant differentially methylated positions were observed in the higher vs lower PFAS profile (FDR p-value < 0.05). These PFAS-associated CpG sites annotated to gene regions related to various cancers, cognition, and cardiometabolic health. We identified 17 pathways (FDR p-value < 0.05), which indicate possible mechanism linking PFAS exposure to several health effects.