Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure.

ABSTRACT: BACKGROUND:Chronic exposure to arsenic (As), a human toxicant and carcinogen, remains a global public health problem. Health risks persist after As exposure has ended, suggesting epigenetic dysregulation as a mechanistic link between exposure and health outcomes. OBJECTIVES:We investigated the association between total urinary As and locus-specific DNA methylation in the Strong Heart Study, a cohort of American Indian adults with low-to-moderate As exposure [total urinary As, mean?(±SD)??g/g creatinine: 11.7 (10.6)]. METHODS:DNA methylation was measured in 2,325 participants using the Illumina MethylationEPIC array. We implemented linear models to test differentially methylated positions (DMPs) and the DMRcate method to identify regions (DMRs) and conducted gene ontology enrichment analysis. Models were adjusted for estimated cell type proportions, age, sex, body mass index, smoking, education, estimated glomerular filtration rate, and study center. Arsenic was measured in urine as the sum of inorganic and methylated species. RESULTS:In adjusted models, methylation at 20 CpGs was associated with urinary As after false discovery rate (FDR) correction (FDR

SUBMITTER: Bozack AK 

PROVIDER: S-EPMC7534587 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature