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Children's Health Advance Publication

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Environ Health Perspect; DOI:10.1289/ehp.1510437

Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA)

Benjamin B. Green1,2,3, Margaret R. Karagas1,3, Tracy Punshon4, Brian P. Jackson5, David J. Robbins6, E. Andres Houseman7, and Carmen J. Marsit1,2,3
Author Affiliations open
1Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA; 2Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA; 3Children’s Environmental Health and Disease Prevention Research Center at Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA; 4Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire, USA; 5Department of Earth Sciences, Dartmouth College, Hanover, New Hampshire, USA; 6Molecular Oncology Program, The DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; 7School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA

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  • Background: 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 impact fetal, newborn, and infant health resulting in a range of phenotypic outcomes.

    Objectives: 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.

    Methods: Linear regression models using a reference-free correction to account for cellular composition were employed to determine CpG loci affected by arsenic levels.

    Results: Total arsenic measured in maternal urine during the second trimester was not associated with methylation in the placenta, while arsenic levels quantified through maternal toenail collected at birth were associated with methylation at a single CpG loci (p = 4.1×10-8). Placenta arsenic levels were associated with 163 differentially methylated loci (FDR < 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.

    Conclusions: These data demonstrate the potential for arsenic, even at levels commonly experienced in a US 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 impact long-term children’s health.

  • This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

    Citation: Green BB, Karagas MR, Punshon T, Jackson BP, Robbins DJ, Houseman EA, Marsit CJ. Epigenome-Wide Assessment of DNA Methylation in the Placenta and Arsenic Exposure in the New Hampshire Birth Cohort Study (USA). Environ Health Perspect;

    Received: 7 July 2015
    Accepted: 18 December 2015
    Advance Publication: 15 January 2016

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