TY - JOUR
T1 - Prenatal particulate air pollution and DNA methylation in newborns
T2 - An epigenome-wide meta-analysis
AU - Gruzieva, Olena
AU - Xu, Cheng Jian
AU - Yousefi, Paul
AU - Relton, Caroline
AU - Merid, Simon Kebede
AU - Breton, Carrie V.
AU - Gao, Lu
AU - Volk, Heather E.
AU - Feinberg, Jason I.
AU - Ladd-Acosta, Christine
AU - Bakulski, Kelly
AU - Auffray, Charles
AU - Lemonnier, Nathanaël
AU - Plusquin, Michelle
AU - Ghantous, Akram
AU - Herceg, Zdenko
AU - Nawrot, Tim S.
AU - Pizzi, Costanza
AU - Richiardi, Lorenzo
AU - Rusconi, Franca
AU - Vineis, Paolo
AU - Kogevinas, Manolis
AU - Felix, Janine F.
AU - Duijts, Liesbeth
AU - Den Dekker, Herman T.
AU - Jaddoe, Vincent W.V.
AU - Ruiz, José L.
AU - Bustamante, Mariona
AU - Antó, Josep Maria
AU - Sunyer, Jordi
AU - Vrijheid, Martine
AU - Gutzkow, Kristine B.
AU - Grazuleviciene, Regina
AU - Hernandez-Ferrer, Carles
AU - Annesi-Maesano, Isabella
AU - Lepeule, Johanna
AU - Bousquet, Jean
AU - Bergström, Anna
AU - Kull, Inger
AU - Söderhäll, Cilla
AU - Kere, Juha
AU - Gehring, Ulrike
AU - Brunekreef, Bert
AU - Just, Allan C.
AU - Wright, Rosalind J.
AU - Peng, Cheng
AU - Gold, Diane R.
AU - Kloog, Itai
AU - Demeo, Dawn L.
AU - Pershagen, Göran
AU - Koppelman, Gerard H.
AU - London, Stephanie J.
AU - Baccarelli, Andrea A.
AU - Melén, Erik
N1 - Publisher Copyright:
© 2019, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2019/5
Y1 - 2019/5
N2 - 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<2:5 lm (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. https://doi.org/10.1289/EHP4522.
AB - 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<2:5 lm (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. https://doi.org/10.1289/EHP4522.
UR - https://www.scopus.com/pages/publications/85067304041
U2 - 10.1289/EHP4522
DO - 10.1289/EHP4522
M3 - Article
C2 - 31148503
AN - SCOPUS:85067304041
SN - 0091-6765
VL - 127
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 5
M1 - 057012
ER -