Prenatal arsenic exposure and the epigenome: Identifying sites of 5-methyl cytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes

Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease later in life. Here we examined newborn cord blood leukocyte samples from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Changes in iAs-associated DNA methylation were compared to corresponding gene expression levels and birth outcomes. 2,705 genes were identified with iAs-associated differences in DNA methylation. In contrast to minimal association genome-wide, site-specific analyses identified DNA methylation changes that were most predictive of gene expression levels. 16 genes were identified with correlated iAs-associated changes in DNA methylation and mRNA expression, and with enrichment for binding sites of several transcription factors. Furthermore, DNA methylation levels were associated with birth outcomes. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyses coupled to epigenetic assessments.Master of Scienc