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

Environmental Health Perspectives
Benjamin B GreenCarmen J Marsit

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 < 0.0...Continue Reading

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Datasets Mentioned

BETA
GSE71678

Methods Mentioned

BETA
Chip
PCA
PCR
Assay
two-hybrid

Software Mentioned

R
minfi
funNorm
BeadStudio methylation
R package RefFreeEWAS
RefFreeEWAS
R Core Team

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