DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.

dc.contributor.author

Fuemmeler, Bernard F

dc.contributor.author

Dozmorov, Mikhail G

dc.contributor.author

Do, Elizabeth K

dc.contributor.author

Zhang, Junfeng Jim

dc.contributor.author

Grenier, Carole

dc.contributor.author

Huang, Zhiqing

dc.contributor.author

Maguire, Rachel L

dc.contributor.author

Kollins, Scott H

dc.contributor.author

Hoyo, Cathrine

dc.contributor.author

Murphy, Susan K

dc.date.accessioned

2021-07-01T14:54:58Z

dc.date.available

2021-07-01T14:54:58Z

dc.date.issued

2021-05-19

dc.date.updated

2021-07-01T14:54:57Z

dc.description.abstract

Background

Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.

Objective

This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.

Methods

Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure.

Results

Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44).

Discussion

Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.
dc.identifier.issn

0091-6765

dc.identifier.issn

1552-9924

dc.identifier.uri

https://hdl.handle.net/10161/23417

dc.language

eng

dc.publisher

Environmental Health Perspectives

dc.relation.ispartof

Environmental health perspectives

dc.relation.isversionof

10.1289/ehp8099

dc.title

DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.

dc.type

Journal article

duke.contributor.orcid

Zhang, Junfeng Jim|0000-0003-3759-6672

duke.contributor.orcid

Kollins, Scott H|0000-0001-6847-6935

duke.contributor.orcid

Murphy, Susan K|0000-0001-8298-7272

pubs.begin-page

57010

pubs.issue

5

pubs.organisational-group

School of Medicine

pubs.organisational-group

Environmental Sciences and Policy

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Pathology

pubs.organisational-group

Duke

pubs.organisational-group

Nicholas School of the Environment

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Psychology and Neuroscience

pubs.organisational-group

Duke Clinical Research Institute

pubs.organisational-group

Trinity College of Arts & Sciences

pubs.publication-status

Published

pubs.volume

129

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy An Epigenome-Wide Associat.pdf
Size:
548.8 KB
Format:
Adobe Portable Document Format