Title: Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis.
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; Bakulski, Kelly; Auffray, Charles; Lemonnier, Nathanaël; Plusquin, Michelle; Ghantous, Akram; Herceg, Zdenko; Nawrot, Tim S; Pizzi, Costanza; Richiardi, Lorenzo; Rusconi, Franca; Vineis, Paolo; Kogevinas, Manolis; Felix, Janine F; Duijts, Liesbeth; den Dekker, Herman T; Jaddoe, Vincent W V; Ruiz, José L; Bustamante, Mariona; Antó, Josep Maria; Sunyer, Jordi; Vrijheid, Martine; Gutzkow, Kristine B; Grazuleviciene, Regina; Hernandez-Ferrer, Carles; Annesi-Maesano, Isabella; Lepeule, Johanna; Bousquet, Jean; Bergström, Anna; Kull, Inger; Söderhäll, Cilla; Kere, Juha; Gehring, Ulrike; Brunekreef, Bert; Just, Allan C; Wright, Rosalind J; Peng, Cheng; Gold, Diane R; Kloog, Itai; DeMeo, Dawn L; Pershagen, Göran; Koppelman, Gerard H; London, Stephanie J; Baccarelli, Andrea A; Melén, Erik
Published In Environ Health Perspect, (2019 05)
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.
PubMed ID: 31148503
MeSH Terms: 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