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

Gruzieva, Olena; Kogevinas, Manolis; Ruiz, José L.; Bustamante Pineda, Mariona; Antó i Boqué, Josep Maria; Sunyer Deu, Jordi; Vrijheid, Martine; Hernandez-Ferrer, Carles, 1987-; Melén, Erik

doi:http://dx.doi.org/10.1289/EHP4522

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

Citation

Gruzieva O, Xu CJ, Yousefi P, Relton C6, Merid SK, Breton CV et al. Prenatal particulate air pollution and DNA methylation in newborns: an epigenome-wide meta-analysis. Environ Health Perspect. 2019 May;127(5):57012. DOI: 10.1289/EHP4522

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.