Epigenome-wide association study of gestational exposure to organophosphate esters and replacement brominated flame...

DNA methylation (DNAm) has been proposed to mediate the associations of gestational exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with health outcomes. However, there have not been previous epigenome-wide association studies (EWAS) on the impact of prenatal exposure to these chemicals on newborn DNAm.

In 252 pregnant women recruited to the Health Outcomes and Measures of Environment (HOME) Study from 2003 to 2006 in Cincinnati, Ohio, we measured the house dust concentrations of 4 OPEs and 2 RBFRs at 20 weeks of gestation and 3 urinary OPE metabolites at 16 and 26 weeks of gestation and at delivery. DNAm was assessed in newborn cord blood using the Infinium MethylationEPIC BeadChip. Multiple testing was controlled for using false discovery rate (FDR) P-values <0.05 for significance.

Dust tris(1,3-dichloroisopropyl) phosphate was associated with increased methylation in GUK1 (cg12796841). Dust bis(2-ethylhexyl) tetrabromophthalate was associated with decreased methylation in FAM159B (cg12662072) and increased methylation in ATXN10 (cg07527826). Dust OPEs and RBFRs were associated with differentially methylated regions (DMRs) overlapping with genes involved in parturition and emotions (OXT), embryogenesis (HOXB genes), inflammation and immunity (ALOX12), cell signaling (LRRC34), spermatogenesis (BOLL), and tumorigenesis (HOXB genes, DIP2C, RASSF9, FAM118A). Urinary OPEs were associated with DMRs overlapping with DNA repair (MACROD1), stem cell pluripotency (POU5F1) and T-cell development (TCL1A) genes.

Prenatal OPE and RBFR exposure is associated with altered newborn DNAm. Future studies should determine if these alterations lead to disease later in life.