title: Prenatal mercury concentration is associated with changes in DNA methylation at TCEANC2 in newborns.
abstract: BACKGROUND
  Human exposure to the widespread environmental contaminant mercury is a known risk factor for common diseases such as cancer, cardiovascular disease and neurological disorders through poorly characterized mechanisms. Evidence suggests mercury exposure may alter DNA methylation levels, but to date, the effects in early life on a genome-wide scale have not been investigated.
  
  
  METHODS
  A study sample of 141 newborns was recruited in Baltimore, MD, USA and total mercury and methylmercury were measured in cord blood samples. We quantified genome-wide DNA methylation data using CHARM 2.0, an array-based method, and used region-finding analyses to identify concentration-associated differentially methylated regions (DMRs). To test for replication of these identified DMRs in the pilot, or Vanguard, phase of the National Children's Study (NCS), we compared bisulfite-pyrosequenced DNA at candidate regions from 85 whole cord blood samples with matched first trimester maternal mercury concentration measures.
  
  
  RESULTS
  Total mercury concentration was associated with methylation at DMRs inside ANGPT2 and near PRPF18 genes [false discovery rate (FDR) < 0.05], as well as DMRs near FOXD2 and within TCEANC2 (FDR< 0.1) genes. Methylmercury concentration was associated with an overlapping DMR within TCEANC2 (FDR< 0.05). In NCS replication analyses, methylation levels at three of four cytosine-guanine DNA dinucleotides (CpG sites) within the TCEANC2 DMR were associated with total mercury concentration (P < 0.05), and this association was diminished after adjusting for estimated cell proportions.
  
  
  CONCLUSIONS
  Evidence for an association between mercury and DNA methylation at the TCEANC2 region was found, which may represent a mercury-associated shift in cord blood cell composition or a change in methylation within blood cell types. Further confirmatory studies are needed.
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Bakulski
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: HwaJin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jason I
authors.initials: JI
authors.lastname: Feinberg
authors.affiliation: Purdue University, School of Health Sciences, West Lafayette, Indiana, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wells
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Brown
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA, Columbia University Mailman School of Public Health, New York City, New York, USA.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Herbstman
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Witter
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Arizona State University, Fulton School of Engineering, Tempe, Arizona, USA.
authors.forename: Rolf U
authors.initials: RU
authors.lastname: Halden
authors.affiliation: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Caldwell
authors.affiliation: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Mortensen
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Lieber Institute for Brain Development, Baltimore, Maryland, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Jaffe
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA and.
authors.forename: John
authors.initials: J
authors.lastname: Moye
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Caulfield
authors.affiliation: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA, George Washington University School of Public Health, Washington D.C., USA.
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldman
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, dfallin@jhu.edu.
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
mesh_terms: D000328:Adult; D015142:Baltimore; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008628:Mercury / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D035602:Transcriptional Elongation Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D035602:Transcriptional Elongation Factors; D008628:Mercury
keywords: DNA methylation; cord blood; epigenetics; mercury exposure; methylmercury