Effects of Prenatal Air Pollution on Family-Specific, Genome-Wide, Repetitive Element Methylation in Cord Blood
Year: 2019
Type: conference-abstract
Abstract: OPS 48: Air pollution and epigenetics, Room 417, Floor 4, August 26, 2019, 4:30 PM - 5:30 PM Background/Objective: Repetitive elements (REs) comprise more than 50% of the genome and methylation suppresses their transpositions (insertions into other genomic regions) that can damage DNA. Global average RE methylation is inversely associated with particulate matter ≤2.5µm (PM2.5) exposure, however, averaging all RE methylation may overlook their biological activity, as RE subfamilies and individual REs vary in methylation. We employed a method predicting genome-wide, RE subfamily-specific, methylation in cord blood and investigated their associations with prenatal PM2.5 exposure. Methods: Trimester average PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and residence location of 443 women from the PROGRESS birth-cohort in Mexico City. We measured cord blood DNA methylation with the Illumina EPICArray using a random forest-based algorithm to predict genome-wide, locus-specific CpG methylation of long interspersed elements-1 (L1) and a short interspersed element (Alu) using nearby CpG sites. We modeled associations between PM2.5 with: 1) methylation of subfamilies within the most recent L1PA, L1PB, and Alu lineages averaged across the genome; and 2) genomic locus-specific aggregates of 2 or more adjacent RE CpGs from these subfamilies. Results: We imputed methylation of 1,183 CpG aggregates and 25 subfamilies within the L1PA and L1PB lineages and 69,596 aggregates and 36 Alu subfamilies with mean methylation of 92%. Average methylation of 20 L1 and 35 Alu subfamilies was inversely associated with 2nd trimester PM2.5. Restricting analysis to full-length L1, methylation of L1PA2, L1PA3, L1PA5, and the active element, L1HS, were inversely associated with PM2.5 in the 2nd and 3rd trimester. Investigations of individual CpGs yielded two aggregates associated with PM2.5 after multiple comparison corrections. Conclusions: Reduced RE subfamily methylation may promote transpositions and cell toxicity that could be related to health endpoints such as cancer. Future work will investigate RE expression and whether RE methylation/expression mediate relationships between PM2.5 exposure and health.
Source: Environmental Epidemiology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,200
OpenAlex ID: W2981453595