DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life

Abstract

Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight. Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 mu m (PM10). This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPosOMICS birth cohort consortium including cord blood from ENVIRON-AGE (n = 197), INMA (n = 84), Piccolipiu (n = 99) and Rhea (n = 75). We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methlation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years. The CpG cg21785536 was inversly associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 mu g/m(3); raw p-value = 3.82 X 10(-8)). Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1. We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.