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Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Olena Gruzieva 1, 2 Cheng-Jian Xu 3 Paul yousefi 4 Caroline Relton 4 Simon Kebede Merid 1 Carrie Breton 5 Lu Gao 5 Heather Volk 6 Jason Feinberg 6 Christine Ladd-Acosta 7 Kelly Bakulski 7 Charles Auffray 8 Nathanaël Lemonnier 8, 9 Michelle Plusquin 10, 11 Akram Ghantous 12 Zdenko Herceg 12 Tim Nawrot 10, 13 Costanza Pizzi 14 Lorenzo Richiardi 14 Franca Rusconi 15 Paolo Vineis 11 Manolis Kogevinas 16, 17 Janine Felix 18 Liesbeth Duijts 18 Herman den Dekker 18 Vincent Jaddoe 18 José Ruiz 19, 20 Mariona Bustamante 16, 17, 19 Josep Maria Antó 16, 17, 21 Jordi Sunyer 16, 17, 21 Martine Vrijheid 16, 17 Kristine Gutzkow 22 Regina Grazuleviciene 23 Carles Hernandez-Ferrer 16, 24 Isabella Annesi-Maesano 25 Johanna Lepeule 9 Jean Bousquet 26, 27 Anna Bergström 1, 2 Inger Kull 1, 28 Cilla Söderhäll 1 Juha Kere 1, 29 Ulrike Gehring 30 Bert Brunekreef 30 Allan Just 31 Rosalind Wright 31 Cheng Peng 32 Diane Gold 32, 33 Itai Kloog 34 Dawn Demeo 32 Göran Pershagen 1, 2 Gerard Koppelman 3 Stephanie London 35 Andrea Baccarelli 36 Erik Melén 1, 28 
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 <10 (PM10) or <2.5μm (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.
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Submitted on : Tuesday, June 1, 2021 - 3:02:16 PM
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Olena Gruzieva, Cheng-Jian Xu, Paul yousefi, Caroline Relton, Simon Kebede Merid, et al.. Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis. Environmental Health Perspectives, National Institute of Environmental Health Sciences, 2019, 127 (5), pp.057012. ⟨10.1289/EHP4522⟩. ⟨inserm-03179361⟩



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