title: Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA).
abstract: Arsenic is one of the most commonly encountered environmental toxicants, and research from model systems has suggested that one mode of its toxic activity may be through alterations in DNA methylation. In utero exposure to arsenic can affect fetal, newborn, and infant health, resulting in a range of phenotypic outcomes.
  
  
  
  This study examined variation in placental DNA methylation and its relationship to arsenic exposure in 343 individuals enrolled in the New Hampshire Birth Cohort Study.
  
  
  
  Linear regression models using a reference-free correction to account for cellular composition were employed to determine CpG loci affected by arsenic levels.
  
  
  
  Total arsenic measured in maternal urine during the second trimester was not associated with methylation in the placenta, whereas arsenic levels quantified through maternal toenail collected at birth were associated with methylation at a single CpG locus (p = 4.1 × 10-8). Placenta arsenic levels were associated with 163 differentially methylated loci (false discovery rate < 0.05), with 11 probes within the LYRM2 gene reaching genome-wide significance (p < 10-8). Measurement of LYRM2 mRNA levels indicated that methylation was weakly to moderately correlated with expression (r = 0.15, p < 0.06). In addition, we identified pathways suggesting changes in placental cell subpopulation proportions associated with arsenic exposure.
  
  
  
  These data demonstrate the potential for arsenic, even at levels commonly experienced in a U.S. population, to have effects on the DNA methylation status of specific genes in the placenta and thus supports a potentially novel mechanism for arsenic to affect long-term children's health.
  
  
  
  Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. 2016. Epigenome-wide assessment of DNA methylation in the placenta and arsenic exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect 124:1253-1260; http://dx.doi.org/10.1289/ehp.1510437.
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Green
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Tracy
authors.initials: T
authors.lastname: Punshon
authors.forename: Brian P
authors.initials: BP
authors.lastname: Jackson
authors.forename: David J
authors.initials: DJ
authors.lastname: Robbins
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D001724:Birth Weight; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D009513:New Hampshire / Q000453:epidemiology; D010920:Placenta / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology
chemical_list: D015386:Hazardous Substances; D001151:Arsenic