title: Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.
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.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olena
authors.initials: O
authors.lastname: Gruzieva
authors.forename: Cheng-Jian
authors.initials: CJ
authors.lastname: Xu
authors.forename: Carrie V
authors.initials: CV
authors.lastname: Breton
authors.forename: Isabella
authors.initials: I
authors.lastname: Annesi-Maesano
authors.forename: Josep M
authors.initials: JM
authors.lastname: Antó
authors.forename: Charles
authors.initials: C
authors.lastname: Auffray
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ballereau
authors.forename: Tom
authors.initials: T
authors.lastname: Bellander
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Charles
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Kluizenaar
authors.forename: Herman T
authors.initials: HT
authors.lastname: den Dekker
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Duijts
authors.forename: Janine F
authors.initials: JF
authors.lastname: Felix
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gehring
authors.forename: Mònica
authors.initials: M
authors.lastname: Guxens
authors.forename: Vincent V W
authors.initials: VV
authors.lastname: Jaddoe
authors.forename: Soesma A
authors.initials: SA
authors.lastname: Jankipersadsing
authors.forename: Simon Kebede
authors.initials: SK
authors.lastname: Merid
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.forename: Nathanael
authors.initials: N
authors.lastname: Lemonnier
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.forename: Wenche
authors.initials: W
authors.lastname: Nystad
authors.forename: Christian Magnus
authors.initials: CM
authors.lastname: Page
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Panasevich
authors.forename: Dirkje
authors.initials: D
authors.lastname: Postma
authors.forename: Rémy
authors.initials: R
authors.lastname: Slama
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Göran
authors.initials: G
authors.lastname: Pershagen
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
mesh_terms: D000393:Air Pollutants / Q000032:analysis*; D000397:Air Pollution / Q000706:statistics & numerical data*; D002648:Child; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008131:London; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D009585:Nitrogen Dioxide / Q000032:analysis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*
chemical_list: D000393:Air Pollutants; D009585:Nitrogen Dioxide