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 ( ${\text{NO}}_2$ ) and particulate matter ( ${\mathrm{PM}}_{2.5}$ , fine particulate matter with aerodynamic diameter $\le 2.5\mathrm{\mu }\mathrm{m}$ ; ${\mathrm{PM}}_{10}$ , particulate matter with aerodynamic diameter $\le 10\mathrm{\mu }\mathrm{m}$ ) and ${\mathrm{PM}}_{2.5\text{absorbance}}$ , 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 ${\text{NO}}_2$ exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold $p<1.19\times {10}^{-7}$ ) or for 4,980 CpG sites (False Discovery $\text{Rate}<0.05$ ). 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 ${\text{NO}}_2$ 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 ${\text{NO}}_2-\text{exposure}$ –related respiratory disease. https://doi.org/10.1289/EHP2045