Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

Olena Gruzieva*, Cheng-Jian Xu, Carrie V. Breton, Isabella Annesi-Maesano, Josep M. Anto, Charles Auffray, Stephane Ballereau, Tom Bellander, Jean Bousquet, Mariona Bustamante, Marie-Aline Charles, Yvonne de Kluizenaar, Herman T. den Dekker, Liesbeth Duijts, Janine F. Felix, Ulrike Gehring, Monica Guxens, Vincent V. W. Jaddoe, Soesma A. Jankipersadsing, Simon Kebede MeridJuha Kere, Ashish Kumar, Nathanael Lemonnier, Johanna Lepeule, Wenche Nystad, Christian Magnus Page, Sviatlana Panasevich, Dirkje Postma, Remy Slama, Jordi Sunyer, Cilla Soderhall, Jin Yao, Stephanie J. London, Goran Pershagen, Gerard H. Koppelman, Erik Melen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 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.

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.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalEnvironmental Health Perspectives
Volume125
Issue number1
DOIs
Publication statusPublished - Jan-2017

Keywords

  • POLYCYCLIC AROMATIC-HYDROCARBONS
  • DNA METHYLATION
  • QUANTILE NORMALIZATION
  • RESPIRATORY HEALTH
  • OXIDATIVE STRESS
  • MATERNAL SMOKING
  • CORD BLOOD
  • EARLY-LIFE
  • ASTHMA
  • ASSOCIATION

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