title: Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance?
abstract: BACKGROUND
  Maternal smoking in pregnancy is associated with adverse health outcomes in children, including cancers; underlying mechanisms may include epigenetic modifications. Using Illumina's 450K array, we previously identified differential DNA methylation related to maternal smoking during pregnancy at 26 CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect in utero exposure only or possibly epigenetic inheritance of smoking-related modifications is unclear.
  
  
  METHODS
  We therefore evaluated the impact of the timing of mother's smoking (before or during pregnancy using cotinine measured at 18 weeks gestation), the father's smoking before conception, and the grandmother's smoking during her pregnancy with the mother on methylation at these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting for covariates, applying Bonferroni correction.
  
  
  RESULTS
  The strongest and only statistically significant associations were observed for sustained smoking by the mother during pregnancy through at least gestational week 18 (P < 1.6 × 10(-5) for all 26 CpGs). We observed no statistically significant differential methylation due to smoking by the mother before pregnancy or that ceased by week 18, father's smoking before conception, or grandmother's smoking while pregnant with the mother.
  
  
  CONCLUSIONS
  Differential methylation at these CpGs in newborns seems to reflect sustained in utero exposure rather than epigenetic inheritance.
  
  
  CONCLUSIONS
  Smoking cessation in early pregnancy may negate effects on methylation. Analyses of maternal smoking during pregnancy and offspring health outcomes, including cancer, limited to ever smoking might miss true associations. Cancer Epidemiol Biomarkers Prev; 23(6); 1007-17. ©2014 AACR.
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Bonnie R
authors.initials: BR
authors.lastname: Joubert
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Siri E
authors.initials: SE
authors.lastname: Håberg
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, NorwayAuthors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Nilsen
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, NorwayAuthors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Oivind
authors.initials: O
authors.lastname: Midttun
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Nystad
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway.
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.affiliation: Authors' Affiliations: Division of Intramural Research, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina; Fred Hutchinson Cancer Research Center, Seattle, Washington; Norwegian Institute of Public Health, Oslo; Haukeland University Hospital; University of Bergen; and Bevital A/S, Laboratoriebygget, Bergen, Norway london2@niehs.nih.gov.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
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