Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation

Green space exposure during pregnancy has been associated with lower risk of adverse birth outcomes, but the biological mechanisms remain unclear. Epigenetic changes, such as DNA methylation (DNAm), may contribute to this association. The placenta, crucial for foetal development, has been understudied in relation to prenatal green space exposure and DNAm on a genome-wide scale. Here, we aimed to investigate the association between green space exposure during pregnancy and epigenome-wide placental DNAm in 550 mother-child pairs from the Barcelona Life Study Cohort (BiSC) in Spain. Green space exposure was assessed as (i) residential surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 300 m and 500 m), (ii) residential distance to the nearest major green space (meters), (iii) use of green space (hours/week), and (iv) visual access to greenery through the home window (≥half of the view). Placental DNAm was measured with the EPIC array. Differentially methylated positions (DMPs) were identified using robust linear regression models adjusted for covariates, while differentially methylated regions (DMRs) were identified using the dmrff method. After Bonferroni correction, cg14852540, annotated to SLC25A10 gene, showed an inverse association with residential greenness within 500 m buffer. Additionally, 101 DMPs were suggestively significant (p-values <1 × 10^-5) and annotated to genes involved in glucocorticoid-related pathways, inflammatory response, oxidative stress response, and oocyte maturation. No DMRs were identified. Overall, we identified an association between residential greenness and DNAm levels at one CpG in the SLC25A10 gene. Larger studies are needed to validate these findings and understand the biological pathways.