Title
Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure
Author
Gruzieva, O.
Xu, C.J.
Breton, C.V.
Annesi-Maesano, I.
Antó, J.M.
Auffray, C.
Ballereau, S.
Bellander, T.
Bousquet, J.
Bustamante, M.
Charles, M.A.
de Kluizenaar, Y.
Den Dekker, H.T.
Duijts, L.
Felix, J.F.
Gehring, U.
Guxens, M.
Jaddoe, V.V.W.
Jankipersadsing, S.A.
Merid, S.K.
Kere, J.
Kumar, A.
Lemonnier, N.
Lepeule, J.
Nystad, W.
Page, C.M.
Panasevich, S.
Postma, D.
Slama, R.
Sunyer, J.
Söderhäll, C.
Yao, J.
London, S.J.
Pershagen, G.
Koppelman, G.H.
Melén, E.
Publication year
2017
Abstract
Background: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. Objectives: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. Methods: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239). Results: We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were alsosignificant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression. Conclusions: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways
Subject
2016 Urban Mobility & Environment
SUMS - Sustainable Urban Mobility and Safety
ELSS - Earth, Life and Social Sciences
To reference this document use:
http://resolver.tudelft.nl/uuid:95807703-b586-4bb6-b0a0-6462dc5dfbba
DOI
https://doi.org/10.1289/ehp36
TNO identifier
577068
Publisher
Public Health Services, US Dept of Health and Human Services
ISSN
0091-6765
Source
Environmental Health Perspectives, 125 (1), 104-110
Document type
article