Maternal Epigenetic Signatures Linking Prenatal Serum PFAS Concentrations to Birth Size in an African American Maternal–Child Cohort
Youran Tan, Anne L. Dunlop, Todd M. Everson, Alicia K. Smith, Stephanie M. Eick, Ziyin Tang, Shudi Pan, Neha Sehgal, Dana Boyd Barr, Kurunthachalam Kannan, P. Barry Ryan, Carmen J. Marsit, Donghai LiangAbstract
Per- and polyfluoroalkyl substance (PFAS) exposures have been linked to reduced birth size, but the underlying epigenetic mechanisms remain unclear. Among 296 mother–infant dyads in the Atlanta African American Maternal–Child Cohort (2016–2020), early pregnancy maternal blood samples (8–14 weeks) were processed for serum PFAS assessment and blood mononuclear cell (PBMC) DNA methylation profiling. We assessed birth size using sex-specific birth weight z-scores (BWZ) and small-for-gestational-age (SGA) status. Individual and mixture PFAS methylation associations were estimated by using robust generalized linear regression and quantile g-computation. We also conducted differentially methylated region (DMR), gene ontology, sex-specific, and exploratory mediation analyses. Overall, 132 CpGs were associated with at least one PFAS (FDR < 0.05), including 34, 60, 32, and 10 linked with PFHxS, PFOS, PFOA, and PFNA, respectively. PFOS showed the largest effects and appeared to drive the mixture associations. Six CpGs (annotated to EVA1A, FCRL1, CTIF, ABHD12, and WDYHV1) were associated with PFAS levels and birth size indicators. We identified 2–9 DMRs associated with individual PFASs and their mixture. Sex-specific PFAS methylation associations were observed. The PFAS-associated genes are involved in the inflammatory response, immune activity, and lipid homeostasis. Prenatal serum PFAS concentrations were associated with alterations in maternal DNA methylation, which in turn were associated with infant birth size.