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

Abstract

Maternal exposure to green space during pregnancy has been associated with lower risk for adverse birth outcomes; however, the underlying biological mechanisms remain largely unknown. Epigenetic changes, such as DNA methylation (DNAm), might be one of the molecular mechanisms contributing to this association. The placenta is the key organ for foetal growth and development, but studies of prenatal green space exposure and placental DNAm are scarce and have not been conducted on a genome-wide scale. Here, we aimed to investigate the association between exposure to green space during pregnancy and epigenome-wide placental DNAm. This study was conducted in 550 mother-child pairs from the Barcelona Life Study Cohort (BiSC), a population-based birth cohort in Spain (2018-2021). We comprehensively assessed green space exposure during pregnancy as (i) residential surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100m, 300m and 500m), (ii) residential distance to the nearest major green space (meters), iii) use of green space (hours/week), and iv) visual access to greenery through home window (≥half of the view). Placental DNAm was measured with the EPIC array. To identify differentially methylated positions (DMPs), we fitted robust linear regression models adjusted for relevant covariates, while differentially methylated regions (DMRs) were identified using the dmrff method. After Bonferroni (BN) correction, cg14852540, annotated to SLC25A10 gene, was inversely associated with residential surrounding greenness within 500m buffer. Additionally, ten unique DMRs were associated with surrounding greenness within 300m and 500m, distance or visual access to green space. No associations were found for surrounding greenness within 100m or use of green space. Genes annotated to these loci are involved in transcriptional regulation, metabolism and mitochondrial respiration. Overall, we identified associations between prenatal green space exposure and DNAm levels in placenta. Further research is needed to validate these results and understand the underlying biological pathways.