title: 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.
abstract: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
  
  
  
  We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
  
  
  
  We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).
  
  
  
  We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10-7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.
  
  
  
  We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Bonnie R
authors.initials: BR
authors.lastname: Joubert
authors.forename: Siri E
authors.initials: SE
authors.lastname: Håberg
authors.forename: Roy M
authors.initials: RM
authors.lastname: Nilsen
authors.forename: Xuting
authors.initials: X
authors.lastname: Wang
authors.forename: Stein E
authors.initials: SE
authors.lastname: Vollset
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Huang
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Lea A
authors.initials: LA
authors.lastname: Cupul-Uicab
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.forename: Wenche
authors.initials: W
authors.lastname: Nystad
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bell
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D009664:Norway / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014481:United States / Q000453:epidemiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D003367:Cotinine; D019363:Cytochrome P-450 CYP1A1; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors; C492162:AHRR protein, human; C498275:GFI1 protein, human; C569463:CYP1A1 protein, human