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

Olena Gruzieva, Cheng Jian Xu, Paul Yousefi, Caroline Relton, Simon Kebede Merid, Carrie V. Breton, Lu Gao, Heather E. Volk, Jason I. Feinberg, Christine Ladd-Acosta, Kelly Bakulski, Charles Auffray, Nathanaël Lemonnier, Michelle Plusquin, Akram Ghantous, Zdenko Herceg, Tim S. Nawrot, Costanza Pizzi, Lorenzo Richiardi, Franca RusconiPaolo Vineis, Manolis Kogevinas, Janine F. Felix, Liesbeth Duijts, Herman T. Den Dekker, Vincent W.V. Jaddoe, José L. Ruiz, Mariona Bustamante, Josep Maria Antó, Jordi Sunyer, Martine Vrijheid, Kristine B. Gutzkow, Regina Grazuleviciene, Carles Hernandez-Ferrer, Isabella Annesi-Maesano, Johanna Lepeule, Jean Bousquet, Anna Bergström, Inger Kull, Cilla Söderhäll, Juha Kere, Ulrike Gehring, Bert Brunekreef, Allan C. Just, Rosalind J. Wright, Cheng Peng, Diane R. Gold, Itai Kloog, Dawn L. Demeo, Göran Pershagen, Gerard H. Koppelman, Stephanie J. London, Andrea A. Baccarelli, Erik Melén

Research output: Contribution to journalArticle

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<2:5 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.

Original languageEnglish (US)
Article number057012
JournalEnvironmental health perspectives
Volume127
Issue number5
DOIs
StatePublished - May 2019

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Air Pollution
DNA Methylation
Meta-Analysis
Newborn Infant
Particulate Matter
Molecular Sequence Annotation
Lung
Cytosine
Guanine
Epigenomics
Asthma
Phosphates
Mothers
Pregnancy
Messenger RNA
Health

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Gruzieva, O., Xu, C. J., Yousefi, P., Relton, C., Merid, S. K., Breton, C. V., ... Melén, E. (2019). Prenatal particulate air pollution and DNA methylation in newborns: An epigenome-wide meta-analysis. Environmental health perspectives, 127(5), [057012]. https://doi.org/10.1289/EHP4522

Prenatal particulate air pollution and DNA methylation in newborns : An epigenome-wide meta-analysis. / 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.

In: Environmental health perspectives, Vol. 127, No. 5, 057012, 05.2019.

Research output: Contribution to journalArticle

Gruzieva, O, Xu, CJ, Yousefi, P, Relton, C, Merid, SK, Breton, CV, Gao, L, Volk, HE, Feinberg, JI, Ladd-Acosta, C, Bakulski, K, Auffray, C, Lemonnier, N, Plusquin, M, Ghantous, A, Herceg, Z, Nawrot, TS, Pizzi, C, Richiardi, L, Rusconi, F, Vineis, P, Kogevinas, M, Felix, JF, Duijts, L, Den Dekker, HT, Jaddoe, VWV, Ruiz, JL, Bustamante, M, Antó, JM, Sunyer, J, Vrijheid, M, Gutzkow, KB, 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, AC, Wright, RJ, Peng, C, Gold, DR, Kloog, I, Demeo, DL, Pershagen, G, Koppelman, GH, London, SJ, Baccarelli, AA & Melén, E 2019, 'Prenatal particulate air pollution and DNA methylation in newborns: An epigenome-wide meta-analysis', Environmental health perspectives, vol. 127, no. 5, 057012. https://doi.org/10.1289/EHP4522
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. / Prenatal particulate air pollution and DNA methylation in newborns : An epigenome-wide meta-analysis. In: Environmental health perspectives. 2019 ; Vol. 127, No. 5.
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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 <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.",
author = "Olena Gruzieva and Xu, {Cheng Jian} and Paul Yousefi and Caroline Relton and Merid, {Simon Kebede} and Breton, {Carrie V.} and Lu Gao and Volk, {Heather E.} and Feinberg, {Jason I.} and Christine Ladd-Acosta and Kelly Bakulski and Charles Auffray and Nathana{\"e}l Lemonnier and Michelle Plusquin and Akram Ghantous and Zdenko Herceg and Nawrot, {Tim S.} and Costanza Pizzi and Lorenzo Richiardi and Franca Rusconi and Paolo Vineis and Manolis Kogevinas and Felix, {Janine F.} and Liesbeth Duijts and {Den Dekker}, {Herman T.} and Jaddoe, {Vincent W.V.} and Ruiz, {Jos{\'e} L.} and Mariona Bustamante and Ant{\'o}, {Josep Maria} and Jordi Sunyer and Martine Vrijheid and Gutzkow, {Kristine B.} and Regina Grazuleviciene and Carles Hernandez-Ferrer and Isabella Annesi-Maesano and Johanna Lepeule and Jean Bousquet and Anna Bergstr{\"o}m and Inger Kull and Cilla S{\"o}derh{\"a}ll and Juha Kere and Ulrike Gehring and Bert Brunekreef and Just, {Allan C.} and Wright, {Rosalind J.} and Cheng Peng and Gold, {Diane R.} and Itai Kloog and Demeo, {Dawn L.} and G{\"o}ran Pershagen and Koppelman, {Gerard H.} and London, {Stephanie J.} and Baccarelli, {Andrea A.} and Erik Mel{\'e}n",
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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

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.

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