You are here:
Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines cohort study.
Citation:
de F.C. Lichtenfels, A., D. van der Plaat, K. de Jong, C. van Diemen, D. Postma, I. Nedeljkovic, C. van Duijn, N. Amin, S. la Bastide-van Gemert, M. de Vries, C. Ward-Caviness, K. Wolf, M. Waldenberger, A. Peters, R. Stolk, B. Brunekreef, H. Boezen, AND J. Vonk. Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines cohort study. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 126(2):027004, (2018).
Impact/Purpose:
This article is the first to show that epigenetic loci associated with long-term exposure to air pollution may mediate associations between air pollution and lung function. This is an important step in understanding the role epigenetics plays in mediating the effects of air pollution on disease.
Description:
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 µdy 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 ≤2.5 µm; PM10, particulate matter with aerodynamic diameter ≤10 µm) and PM2.5absorbance, indicator of elemental carbon content (eimated with land-use regression models) with DNA methylation in whole blood (lllumina® 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 N02 exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold p<1.19x10-7) 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 N02 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.
