1. Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals
- Author
-
Robert O. Wright, Brent A. Coull, Chitra Amarasiriwardena, Diane R. Gold, Sheryl L. Rifas-Shiman, Emily Oken, Andrea A. Baccarelli, Marie-France Hivert, Anne K. Bozack, and Andres Cardenas
- Subjects
Adult ,Clinical Sciences ,Reproductive health and childbirth ,Persistence (computer science) ,Paediatrics and Reproductive Medicine ,Andrology ,Epigenome ,Clinical Research ,Pregnancy ,Prenatal exposure ,Prenatal Diagnosis ,Genetics ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Medicine ,Humans ,Epigenetics ,Aetiology ,Molecular Biology ,Genetics (clinical) ,EWAS ,Pediatric ,Manganese ,DNA methylation ,business.industry ,Research ,Human Genome ,Infant, Newborn ,dNaM ,Infant ,Methylation ,Perinatal Period - Conditions Originating in Perinatal Period ,Newborn ,Fetal Blood ,Metals ,Cord blood ,Prenatal Exposure Delayed Effects ,Cohort ,Female ,business ,Developmental Biology - Abstract
Background Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6–10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR comb-p (Sidak p Results Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10–6). Both associations remained significant but attenuated in blood DNAm collected at mid-childhood (p p Sidak p Conclusions Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.
- Published
- 2021