ABSTRACT Chronic exposure to inorganic arsenic is a global public health concern affecting over 100 million people worldwide. Arguably the largest poisoned population in history, more than 57 million people in Bangladesh are persistently exposed to arsenic by consuming contaminated water. The toxic effects of exposure to arsenic-contaminated drinking water include numerous cancers and non-malignant morbidities; however, variability in the presentation and severity of arsenic-induced diseases exists. Inherited variation has been implicated in susceptibility to arsenic toxicity and the biological response to arsenic exposure. Therefore, efforts to identify genetic determinants of arsenic metabolism efficiency (AME), a key regulator of toxicity risk and outcomes, and susceptibility to arsenic toxicity have been made in the field of genetic epidemiology. Although previous studies identified loci and genetic variants associated with risk of AME and dermatological outcomes, none of these studies focused exclusively on identifying single nucleotide polymorphisms (SNPs) in non-coding RNA regions of the genome associated with the aforementioned traits. For this reason, the main objective of the proposed research is to identify functional variants in non-coding RNA genes associated with susceptibility to arsenic toxicity and characterize their potential functional effects. The aims include identifying SNPs in microRNA-encoding sequences and 3’UTR sequences of messenger RNAs that disrupt microRNA-mRNA interactions, and that are associated with arsenic-induced skin lesion development. Our research strategy includes leveraging existing data from the The Health Effects of Arsenic Longitudinal Study cohort, a group of >8,000 Bangladeshi participants with varying levels of exposure to arsenic-contaminated drinking water. The proposed project will advance our understanding of genetic and environmental susceptibility to dermatological diseases, identify potential therapeutic gene and pathway targets to treat arsenic toxicity, provide insights about processes likely involved in the etiology of arsenic-induced diseases, and inform potential prevention strategies. The goal of the training plan described in the proposal will cultivate expertise in molecular and genetic epidemiology, and environmental health research, while preparing the trainee for an academic research career focused on contributing meaningful knowledge regarding the understudied focus on variants in functional, non-coding elements of the genome.