Prenatal particulate air pollution and DNA methylation in newborns: An epigenome-wide meta-analysis

Olena Gruzieva, Cheng Jian Xu, Paul Yousefi, Caroline Relton, Simon Kebede Merid, Carrie V. Breton, Lu Gao, Heather E. Volk, Jason I. Feinberg, Christine Ladd-Acosta, Kelly Bakulski, Charles Auffray, Nathanaël Lemonnier, Michelle Plusquin, Akram Ghantous, Zdenko Herceg, Tim S. Nawrot, Costanza Pizzi, Lorenzo Richiardi, Franca RusconiPaolo Vineis, Manolis Kogevinas, Janine F. Felix, Liesbeth Duijts, Herman T. Den Dekker, Vincent W.V. Jaddoe, José L. Ruiz, Mariona Bustamante, Josep Maria Antó, Jordi Sunyer, Martine Vrijheid, Kristine B. Gutzkow, Regina Grazuleviciene, Carles Hernandez-Ferrer, Isabella Annesi-Maesano, Johanna Lepeule, Jean Bousquet, Anna Bergström, Inger Kull, Cilla Söderhäll, Juha Kere, Ulrike Gehring, Bert Brunekreef, Allan C. Just, Rosalind J. Wright, Cheng Peng, Diane R. Gold, Itai Kloog, Dawn L. Demeo, Göran Pershagen, Gerard H. Koppelman, Stephanie J. London, Andrea A. Baccarelli, Erik Melén

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter <10 (PM10)or<2:5 lm (PM2:5) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to PM10 (n = 1,949) and PM2:5 (n = 1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associated [false discovery rate (FDR) <0:05] with prenatal PM10 and 14 with PM2:5 exposure. Two of the PM10-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p <0:05) in 7-to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM10 exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM10 and or PM2:5 exposure, of which two PM10-related DMRs, including H19 and MARCH11, replicated in newborns. CONCLUSIONS: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes.

Original languageEnglish
Article number057012
JournalEnvironmental Health Perspectives
Issue number5
StatePublished - 1 May 2019

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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