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

AuthorsGruzieva, O.; Xu, C. J.; Yousefi, P.; Relton, C.; Merid, S. K.; Breton, C. V.; Gao, L.; Volk, H. E.; Feinberg, J. I.; Ladd-Acosta, C.; Bakulski, K.; Auffray, C.; Lemonnier, N.; Plusquin, M.; Ghantous, A.; Herceg, Z.; Nawrot, T. S.; Pizzi, C.; Richiardi, L.; Rusconi, F.; Vineis, P.; Kogevinas, M.; Felix, J. F.; Duijts, L.; Den Dekker, H. T.; Jaddoe, V. W. V.; Ruiz, J. L. ; Bustamante, M.; Antó, Josep M.; Sunyer, J.; Vrijheid, M.; Gutzkow, K.B.; Grazuleviciene, R.; Hernandez-Ferrer, C.; Annesi-Maesano, I.; Lepeule, J.; Bousquet, J.; Bergström, A.; Kull, I.; Söderhäll, C.; Kere, J.; Gehring, U.; Brunekreef, B.; Just, A.C.; Wright, R.J.; Peng, C.; Gold, D.R.; Kloog, I.; Demeo, D.L.
Issue Date2019
PublisherNational Institute of Environmental Health Sciences (U.S.)
CitationEnvironmental Health Perspectives 127 (2019)
AbstractBACKGROUND: 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 (PM)or<2:5 lm (PM) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to PM (n = 1,949) and PM (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 PM and 14 with PM exposure. Two of the PM-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 PM exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM and or PM exposure, of which two PM-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. https://doi.org/10.1289/EHP4522.
Publisher version (URL)http://dx.doi.org/10.1289/EHP4522
Identifiersdoi: 10.1289/EHP4522
issn: 0091-6765
e-issn: 1552-9924
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