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Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure

Gruzieva, Olena and Xu, Cheng-Jian and Breton, Carrie V. and Annesi-Maesano, Isabella and Antó, Josep M. and Auffray, Charles and Ballereau, Stéphane and Bellander, Tom and Bousquet, Jean and Bustamante, Mariona and Charles, Marie-Aline and de Kluizenaar, Yvonne and den Dekker, Herman T. and Duijts, Liesbeth and Felix, Janine F. and Gehring, Ulrike and Guxens, Mònica and Jaddoe, Vincent V. W. and Jankipersadsing, Soesma A. and Merid, Simon Kebede and Kere, Juha and Kumar, Ashish and Lemonnier, Nathanael and Lepeule, Johanna and Nystad, Wenche and Page, Christian Magnus and Panasevich, Sviatlana and Postma, Dirkje and Slama, Rémy and Sunyer, Jordi and Söderhäll, Cilla and Yao, Jin and London, Stephanie J. and Pershagen, Göran and Koppelman, Gerard H. and Melén, Erik. (2017) Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environmental health perspectives, 125 (1). pp. 104-110.

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Abstract

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.; We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.; 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).; 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 also significant 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.; 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. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104-110; http://dx.doi.org/10.1289/EHP36.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Air Pollution and Health (Künzli)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Air Pollution and Health (Künzli)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Kumar, Ashish
Item Type:Article, refereed
Publisher:National Institute of Environmental Health Sciences
ISSN:0091-6765
Note:Publication type according to Uni Basel Research Database: Journal article -- Reproduced with permission from Environmental Health Perspectives
Language:English
Identification Number:
Last Modified:31 Aug 2017 07:43
Deposited On:24 Apr 2017 12:28

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