Children's Health Advance Publication
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)
PDF Version (1.7 MB)
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; http://dx.doi.org/10.1289/ehp.1510437
Received: 7 July 2015
Accepted: 18 December 2015
Advance Publication: 15 January 2016
Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact email@example.com. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
Note to readers with disabilities: EHP has provided a 508-conformant table of contents summarizing the Supplemental Material for this article (see below) so readers with disabilities may determine whether they wish to access the full, nonconformant Supplemental Material. If you need assistance accessing this or any other content on this site, please contact firstname.lastname@example.org. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
Attention, Authors: New Submission System
EHP is now using Editorial Manager for manuscript submissions. All user accounts have been transferred to Editorial Manager—just log into Editorial Manager and reset your password. Editorial Manager offers an in-depth help index; for further questions, contact email@example.com. We hope you enjoy using our streamlined new submission system!
Sign Up to Receive E-mail Alerts
Recent Advance Publications
Urban Dust Microbiome: Impact on Later Atopy and Wheezing
Use of Cooking Fuels and Cataract in a Population-Based Study: The India Eye Disease Study
Particulate Air Pollution and Fasting Blood Glucose in Non-Diabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000-2011
Persistent Organic Pollutants and the Association with Maternal and Infant Thyroid Homeostasis: A Multipollutant Assessment
A Systematic Comparison of Linear Regression-Based Statistical Methods to Assess Exposome-Health Associations