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

Publication ,  Journal Article
Fuemmeler, BF; Dozmorov, MG; Do, EK; Zhang, JJ; Grenier, C; Huang, Z; Maguire, RL; Kollins, SH; Hoyo, C; Murphy, SK
Published in: Environ Health Perspect
May 2021

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.

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Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

May 2021

Volume

129

Issue

5

Start / End Page

57010

Location

United States

Related Subject Headings

  • Toxicology
  • Tobacco Smoke Pollution
  • Pregnancy
  • Maternal Exposure
  • Infant, Newborn
  • Humans
  • Fetal Blood
  • Female
  • Epigenome
  • Epigenesis, Genetic
 

Citation

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Fuemmeler, B. F., Dozmorov, M. G., Do, E. K., Zhang, J. J., Grenier, C., Huang, Z., … Murphy, S. K. (2021). DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study. Environ Health Perspect, 129(5), 57010. https://doi.org/10.1289/EHP8099
Fuemmeler, Bernard F., Mikhail G. Dozmorov, Elizabeth K. Do, Junfeng Jim Zhang, Carole Grenier, Zhiqing Huang, Rachel L. Maguire, Scott H. Kollins, Cathrine Hoyo, and Susan K. Murphy. “DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.Environ Health Perspect 129, no. 5 (May 2021): 57010. https://doi.org/10.1289/EHP8099.
Fuemmeler BF, Dozmorov MG, Do EK, Zhang JJ, Grenier C, Huang Z, et al. DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study. Environ Health Perspect. 2021 May;129(5):57010.
Fuemmeler, Bernard F., et al. “DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.Environ Health Perspect, vol. 129, no. 5, May 2021, p. 57010. Pubmed, doi:10.1289/EHP8099.
Fuemmeler BF, Dozmorov MG, Do EK, Zhang JJ, Grenier C, Huang Z, Maguire RL, Kollins SH, Hoyo C, Murphy SK. DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study. Environ Health Perspect. 2021 May;129(5):57010.

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

May 2021

Volume

129

Issue

5

Start / End Page

57010

Location

United States

Related Subject Headings

  • Toxicology
  • Tobacco Smoke Pollution
  • Pregnancy
  • Maternal Exposure
  • Infant, Newborn
  • Humans
  • Fetal Blood
  • Female
  • Epigenome
  • Epigenesis, Genetic