title: Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood.
abstract: Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3-5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Ladd-Acosta
authors.affiliation: Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.affiliation: Drexel University School of Public Health, Philadelphia, PA, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Drexel University School of Public Health, Philadelphia, PA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gidaya
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Singer
authors.affiliation: National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Schieve
authors.affiliation: Department of Public Health, Institute of Epidemiology and Social Medicine, Department of Economics and Business, National Centre for Register-based Research, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University, Aarhus, Denmark.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Schendel
authors.affiliation: Biomedical Research Informatics Core, Michigan State University, East Lansing, MI, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Jones
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Daniels
authors.affiliation: Division of Environmental and Occupational Disease Control, California Department of Public Health, Richmond, CA, USA.
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Windham
authors.affiliation: Drexel University School of Public Health, Philadelphia, PA, USA; The A.J. Drexel Autism Institute, Drexel University School of Public Health, Philadelphia, PA, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Newschaffer
authors.affiliation: Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Croen
authors.affiliation: Center for Epigenetics, Institute for Basic Biomedical Science, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.affiliation: Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA. Electronic address: dfallin@jhu.edu.
authors.forename: M
authors.initials: M
authors.lastname: Daniele Fallin
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000453:epidemiology*; D060388:Support Vector Machine; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D012906:Smoke
keywords: Biomarker; Childhood; DNA methylation; Epigenetics; Prenatal smoking exposure