Long-term Air Pollution Exposure, Genome-wide DNA Methylation and Lung Function in the LifeLines Cohort Study

Abstract

Background:Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association.Objectives:Our main aim was to study the association between long-term air pollution exposure and DNA methylation.Methods:We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5, fine particulate matter with aerodynamic diameter ≤2.5μm; PM10, particulate matter with aerodynamic diameter ≤10μm) and PM2.5absorbance, indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA).Results:Depending on the p-value threshold used, we found significant associations between NO2 exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold p<1.19×10−7) or for 4,980 CpG sites (False Discovery Rate<0.05). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure.Conclusions:Long-term NO2 exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying NO2-exposure–related respiratory disease. https://doi.org/10.1289/EHP2045

Association between long-term air pollution exposure and DNA methylation: the REGICOR study

“…We initially identified 19 manuscripts (2–10,27–36) based on the search terms and after reading the full manuscripts we finally selected 9 studies (2–10). We selected 12 CpGs showing differential methylation in relation to PM 2.5 from the only manuscript that corrected for Bonferroni criteria (9).…”

“…The most studied epigenetic mechanism is DNA methylation, which is heritable but can also be modified by life-style and environmental factors. Recently, several studies have analyzed the association between air pollution and DNA methylation using a genome-wide approach, and have reported numerous loci showing differential methylation related to this exposure (2–10). The aims of this study were both to identify new genomic loci showing differential methylation associated with long-term exposure to air pollution in a population-based study in Spain and to replicate loci previously reported in other studies.…”

Prolonged exposure to carbon nanoparticles induced methylome remodeling and gene expression in zebrafish heart

“…Hence, given the large distinction in the physical properties of these two carbon nanoparticles (CNPs) it is inappropriate to characterize the toxicity of airborne BC-containing CNPs in in vivo or in vitro studies using industrial CB. Furthermore, as evidenced by accumulating epidemiology and laboratory studies, short-or long-term exposure to fine PM or nanosized materials would induce remarkable changes in the methylation status of whole genome or specific genes in cells or organisms (de F C Lichtenfels et al, 2018;De Nys et al, 2018). Similar links were observed between PM-containing BC exposure and DNA methylation.…”

“…Furthermore, as evidenced by accumulating epidemiology and laboratory studies, short‐ or long‐term exposure to fine PM or nanosized materials would induce remarkable changes in the methylation status of whole genome or specific genes in cells or organisms (de F C Lichtenfels et al, ; De Nys et al, ). Similar links were observed between PM‐containing BC exposure and DNA methylation.…”

Exposure to PM2.5 during pregnancy or lactation increases methylation while reducing the expression of Pdx1 and NEUROG3 in mouse pancreatic islets

“…DNA methylation is currently the most widely investigated epigenetic mechanism and occurs through the addition of a methyl group to a cytosine-guanine dinucleotide (CpG site) [9,10]. Alteration in DNA methylation may be induced by exposure to air pollution, thus altering gene expression patterns [11].…”