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)
1
Karolinska Institutet [Stockholm]
2 Stockholm County Council
3 University of Groningen [Groningen]
4 University of Bristol [Bristol]
5 USC - University of Southern California
6 Johns Hopkins Bloomberg School of Public Health [Baltimore]
7 University of Michigan [Ann Arbor]
8 EISBM - European Institute for Systems Biology and Medicine
9 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
10 UHasselt - Hasselt University
11 Imperial College London
12 IACR - International Agency for Cancer Research
13 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
14 UNITO - Università degli studi di Torino = University of Turin
15 Children’s Hospital A. Meyer [Florence, Italy]
16 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
17 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
18 Erasmus MC - Erasmus University Medical Center [Rotterdam]
19 CRG-UPF - Center for Genomic Regulation
20 CSIC - Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain]
21 IMIM - Hospital del Mar Medical Research Institute [Barcelone, Espagne]
22 NIPH - Norwegian Institute of Public Health [Oslo]
23 VDU - Vytautas Magnus University - Vytauto Didziojo Universitetas
24 Boston Children's Hospital
25 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
26 MACVIA-LR - Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon
27 VIMA - Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique
28 Sachs’ Children and Youth Hospital [Stockholm, Sweden]
29 King‘s College London
30 Universiteit Utrecht / Utrecht University [Utrecht]
31 MSSM - Icahn School of Medicine at Mount Sinai [New York]
32 HMS - Harvard Medical School [Boston]
33 Harvard T.H. Chan School of Public Health
34 BGU - Ben-Gurion University of the Negev
35 NIEHS-NIH - National Institute of Environmental Health Sciences [Durham, NC, USA]
36 Columbia University [New York]
2 Stockholm County Council
3 University of Groningen [Groningen]
4 University of Bristol [Bristol]
5 USC - University of Southern California
6 Johns Hopkins Bloomberg School of Public Health [Baltimore]
7 University of Michigan [Ann Arbor]
8 EISBM - European Institute for Systems Biology and Medicine
9 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
10 UHasselt - Hasselt University
11 Imperial College London
12 IACR - International Agency for Cancer Research
13 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
14 UNITO - Università degli studi di Torino = University of Turin
15 Children’s Hospital A. Meyer [Florence, Italy]
16 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
17 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
18 Erasmus MC - Erasmus University Medical Center [Rotterdam]
19 CRG-UPF - Center for Genomic Regulation
20 CSIC - Consejo Superior de Investigaciones Cientificas [España] = Spanish National Research Council [Spain]
21 IMIM - Hospital del Mar Medical Research Institute [Barcelone, Espagne]
22 NIPH - Norwegian Institute of Public Health [Oslo]
23 VDU - Vytautas Magnus University - Vytauto Didziojo Universitetas
24 Boston Children's Hospital
25 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
26 MACVIA-LR - Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon
27 VIMA - Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique
28 Sachs’ Children and Youth Hospital [Stockholm, Sweden]
29 King‘s College London
30 Universiteit Utrecht / Utrecht University [Utrecht]
31 MSSM - Icahn School of Medicine at Mount Sinai [New York]
32 HMS - Harvard Medical School [Boston]
33 Harvard T.H. Chan School of Public Health
34 BGU - Ben-Gurion University of the Negev
35 NIEHS-NIH - National Institute of Environmental Health Sciences [Durham, NC, USA]
36 Columbia University [New York]
Olena Gruzieva
- Fonction : Auteur
- PersonId : 791623
- ORCID : 0000-0003-4147-5654
Paul Yousefi
- Fonction : Auteur
- PersonId : 806402
- ORCID : 0000-0003-3284-3240
Franca Rusconi
- Fonction : Auteur
- PersonId : 773966
- ORCID : 0000-0002-9544-6472
Janine Felix
- Fonction : Auteur
- PersonId : 801129
- ORCID : 0000-0002-9801-5774
Mariona Bustamante
- Fonction : Auteur
- PersonId : 791009
- ORCID : 0000-0003-0127-2860
Josep Maria Antó
- Fonction : Auteur
Jordi Sunyer
- Fonction : Auteur
Martine Vrijheid
- Fonction : Auteur
- PersonId : 763761
- ORCID : 0000-0002-7090-1758
- IdRef : 225451581
Kristine Gutzkow
- Fonction : Auteur
- PersonId : 806114
- ORCID : 0000-0002-6716-5921
Isabella Annesi-Maesano
- Fonction : Auteur
- PersonId : 754596
- IdHAL : isabella-annesi-maesano
- ORCID : 0000-0002-6340-9300
- IdRef : 123241847
Ulrike Gehring
- Fonction : Auteur
- PersonId : 762120
- ORCID : 0000-0003-3612-5780
- IdRef : 10646633X
Bert Brunekreef
- Fonction : Auteur
- PersonId : 759234
- ORCID : 0000-0001-9908-0060
Allan Just
- Fonction : Auteur
- PersonId : 806403
- ORCID : 0000-0003-4312-5957
Stephanie London
- Fonction : Auteur
- PersonId : 759648
- ORCID : 0000-0003-4911-5290
Andrea Baccarelli
- Fonction : Auteur
- PersonId : 756587
- ORCID : 0000-0002-3436-0640
Résumé
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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