Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure

Milan N Parikh; Cole Brokamp; Erika Rasnick; Lili Ding; Tesfaye B Mersha; Katherine Bowers; Alonzo T Folger

doi:10.1097/EE9.0000000000000227

Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM_2.5 exposure

Environ Epidemiol. 2022 Oct 3;6(5):e227. doi: 10.1097/EE9.0000000000000227. eCollection 2022 Oct.

Authors

Milan N Parikh¹, Cole Brokamp^{1

2}, Erika Rasnick¹, Lili Ding^{1

2}, Tesfaye B Mersha^{2

3}, Katherine Bowers^{1

2}, Alonzo T Folger^{1

2}

Affiliations

¹ Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
³ Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Abstract

Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM_2.5) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM_2.5 affects physiology could be through altering DNA methylation (DNAm). Considering that exposures during specific windows of gestation may have unique effects on DNAm, we hypothesized a timing-specific association between PM_2.5 exposure during pregnancy and DNAm in the neonatal epithelial-cell epigenome.

Methods: After collecting salivary samples from a cohort of 91 neonates, DNAm was assessed at over 850,000 cytosine-guanine dinucleotide (CpG) methylation sites on the epigenome using the MethylationEPIC array. Daily ambient PM_2.5 concentrations were estimated based on the mother's address of primary residence during pregnancy. PM_2.5 was averaged over the first two trimesters, separately and combined, and tested for association with DNAm through an epigenome-wide association (EWA) analysis. For each EWA, false discovery rate (FDR)-corrected P < 0.05 constituted a significant finding and every CpG site with uncorrected P < 0.0001 was selected to undergo pathway and network analysis to identify molecular functions enriched by them.

Results: Our analysis showed that cg18705808 was associated with the combined average of PM_2.5. Pathway and network analysis revealed little similarity between the first two trimesters. Previous studies reported that TMEM184A, the gene regulated by cg18705808, has a putative role in inflammatory pathways.

Conclusions: The differences in pathway and network analyses could potentially indicate trimester-specific effects of PM_2.5 on DNAm. Further analysis with greater temporal resolution would be valuable to fully characterize the effect of PM_2.5 on DNAm and child development.

Keywords: DNA methylation; Fine particulate matter; Prenatal exposure.