Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines Cohort Study
Author(s)
Lichtenfels, Ana Julia de FC
van der plaat, Diana A
de Jong, Kim
van diemen, Cleo C
Postma, Dirkje S
Type
Journal Article
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.
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.
Date Issued
2018-02-01
Date Acceptance
2017-12-13
Citation
Environmental Health Perspectives, 2018, 126 (2)
ISSN
0091-6765
Publisher
The National Institute of Environmental Health Sciences (NIEHS)
Journal / Book Title
Environmental Health Perspectives
Volume
126
Issue
2
Copyright Statement
© 2018 The Author(s). For permissions see: https://ehp.niehs.nih.gov/about-ehp/copyright-permissions
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000424500800004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Environmental Sciences
Public, Environmental & Occupational Health
Toxicology
Environmental Sciences & Ecology
OBSTRUCTIVE PULMONARY-DISEASE
ARTERY ENDOTHELIAL-CELLS
FINE PARTICULATE MATTER
USE REGRESSION-MODELS
ESCAPE PROJECT
EPIGENETIC MEDIATION
NITROGEN-DIOXIDE
PHOSPHOLIPASE-D
BLOOD-PRESSURE
ASSOCIATIONS
Publication Status
Published
Article Number
027004
Date Publish Online
2018-02-06