Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero

This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Taylor & Francis and can be found at: http://www.tandfonline.com/loi/kepi20#.VmDbAUbcjfcExposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n=37), umbilical artery (n=45) and human umbilical vein endothelial cells (HUVEC) (n=52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and four CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F P<0.001), placenta (Max F P