Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals.

Adult DNA Methylation / genetics Epigenome / genetics Female Fetal Blood / chemistry Humans Infant Infant, Newborn Pregnancy Prenatal Diagnosis / methods Prenatal Exposure Delayed Effects / genetics
DNA methylation EWAS Manganese Metals Prenatal exposure

Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
19 11 2021
Historique:
received: 17 09 2021
accepted: 08 11 2021
entrez: 20 11 2021
pubmed: 21 11 2021
medline: 1 2 2022
Statut: epublish

Résumé

Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6-10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs using comb-p (Sidak p < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses. Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10 Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.

Sections du résumé

BACKGROUND
Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6-10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs using comb-p (Sidak p < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses.
RESULTS
Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10
CONCLUSIONS
Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.

Identifiants

DOI: 10.1186/s13148-021-01198-z PMID: 34798907 PMC: PMC8605513
pubmed: 34798907
doi: 10.1186/s13148-021-01198-z
pii: 10.1186/s13148-021-01198-z
pmc: PMC8605513
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

208

Subventions

Organisme : NIEHS NIH HHS
ID : U2C ES026561
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD034568
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031259
Pays : United States
Organisme : NIH HHS
ID : UH3 OD023286
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Anne K Bozack (AK)

Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, 2121 Berkeley Way, Room 5302, Berkeley, CA, 94720, USA.
ORCID: 0000-0003-0046-5767

Sheryl L Rifas-Shiman (SL)

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Brent A Coull (BA)

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

Andrea A Baccarelli (AA)

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA.

Robert O Wright (RO)

Department of Environmental Medicine and Public Health and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, New York City, USA.

Chitra Amarasiriwardena (C)

Department of Environmental Medicine and Public Health and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, New York City, USA.

Diane R Gold (DR)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Emily Oken (E)

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Marie-France Hivert (MF)

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.

Andres Cardenas (A)

Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, 2121 Berkeley Way, Room 5302, Berkeley, CA, 94720, USA. andres.cardenas@berkeley.edu.
Center for Computational Biology, University of California, Berkeley, CA, USA. andres.cardenas@berkeley.edu.

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Classifications MeSH

Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Prenatal metal exposure, cord blood DNA...
Recherchemedicale.com › Phénomènes génétiques › Méthylation de l'ADN › Prenatal metal exposure, cord blood DNA...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › Prenatal metal exposure, cord blood DNA...
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Recherchemedicale.com › Personnes › Tranches d'âge › Nourrisson › Prenatal metal exposure, cord blood DNA...
Recherchemedicale.com › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Prenatal metal exposure, cord blood DNA...
Recherchemedicale.com › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Prenatal metal exposure, cord blood DNA...
Recherchemedicale.com › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic gynécologique et obstétrique › Diagnostic prénatal › Prenatal metal exposure, cord blood DNA...
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