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de F C Lichtenfels, A.J.* ; van der Plaat, D.A.* ; de Jong, K.* ; van Diemen, C.C.* ; Postma, D.S.* ; Nedeljkovic, I.* ; van Duijn, C.M.* ; Amin, N.* ; la Bastide-van Gemert, S.* ; de Vries, M.* ; Ward-Caviness, C.K. ; Wolf, K. ; Waldenberger, M. ; Peters, A. ; Stolk, R.P.* ; Brunekreef, B.* ; Boezen, H.M.* ; Vonk, J.M.*

Long-term air pollution exposure, genome-wide DNA methylation and lung function in the lifelines cohort study.

Environ. Health Perspect. 126:027004 (2018)
Verlagsversion Forschungsdaten DOI
Creative Commons Lizenzvertrag
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 (NO 2 ) and particulate matter (PM 2.5 , fine particulate matter with aerodynamic diameter ≤2.5 lm; PM 10 , particulate matter with aerodynamic diameter ≤10 lm) and PM 2.5absorbance , 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 NO 2 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 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 NO 2 -exposure–related respiratory disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Obstructive Pulmonary-disease; Artery Endothelial-cells; Fine Particulate Matter; Use Regression-models; Escape Project; Epigenetic Mediation; Nitrogen-dioxide; Phospholipase-d; Blood-pressure; Associations
ISSN (print) / ISBN 0091-6765
e-ISSN 1552-9924
Quellenangaben Band: 126, Heft: 2, Seiten: , Artikelnummer: 027004 Supplement: ,
Verlag Research Triangle Park
Verlagsort NC [u.a.]
Begutachtungsstatus Peer reviewed