Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis
Publication date
2019-05
Authors
Gruzieva, Olena
Xu, Cheng-Jian
Yousefi, Paul
Relton, Caroline
Merid, Simon Kebede
Breton, Carrie V
Gao, Lu
Volk, Heather E
Feinberg, Jason I
Ladd-Acosta, Christine
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Advisors
Supervisors
Document Type
Article
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Abstract
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 [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) 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) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] 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 ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] 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.
Keywords
Adolescent, Air Pollutants/adverse effects, Air Pollution/adverse effects, Child, Child, Preschool, DNA Methylation/drug effects, Epigenome, Female, Fetal Blood/chemistry, Humans, Infant, Infant, Newborn, Male, Maternal Exposure/adverse effects, Particulate Matter/adverse effects, Pregnancy, Taverne, SDG 3 - Good Health and Well-being
Citation
Gruzieva, 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, J 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 & Pershagen, G 2019, 'Prenatal Particulate Air Pollution and DNA Methylation in Newborns : An Epigenome-Wide Meta-Analysis', Environmental Health Perspectives, vol. 127, no. 5, pp. 57012. https://doi.org/10.1289/EHP4522