# Arsenic and the Human Genome:  susceptibility and response to exposure

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $618,211

## Abstract

PROJECT SUMMARY
Arsenic contamination of food and drinking water is a serious global health issue in the U.S. and worldwide.
Arsenical skin lesions are a common and early sign of arsenic toxicity, but exposure to arsenic is also
associated with risk for various types of cancer, cardiovascular disease, non-malignant respiratory disease,
and shortened life span. A major focus of epidemiological research on arsenic exposure has been
understanding genetic susceptibility to arsenic toxicity. Genetic studies have discovered roles for both
inherited variation (e.g., AS3MT variants) as well as dynamic features of the genome (i.e., telomere length) in
susceptibility to arsenic toxicity and response to exposure. Additional research is needed to fully understand
these gene-environment relationships. The last decade of research on genetic susceptibility to disease in
humans has clearly demonstrated that large studies with genome-wide measurement are highly likely to deliver
discoveries that are re-producible. Thus, we propose creating a large genomic data resource in the context of
an epidemiological study of arsenic exposure in rural Bangladesh. We will use this resource to identify the
features of the human genome that reflect susceptibility or response to arsenic exposure. Our first goal is to
extend our ongoing work on the genetics of arsenic metabolism efficiency (AME) and GxE (gene-by-
environment interaction) to identify inherited variants that influence arsenic metabolism or arsenic toxicity.
Under this goal, we will investigate the biological mechanisms of arsenic-related variants and evaluate the
utility genetic information for exposure reduction. Achieving this goal will entail activities such as genome-wide
association and heritability studies of AME and arsenical skin lesion risk, genome-wide searches for GxE,
estimating the effects of SNPs on arsenic-related health outcomes, and evaluating the impact of returning
genetic results to participants on exposure-related behaviors. Our second goal is to extend or our work on
arsenic and telomere length to identify additional dynamic features of the genome that reflect biological
response to arsenic or susceptibility to arsenic toxicity. Achieving this goal will entail testing numerous
genomic features for association with arsenic exposure and arsenical skin lesion status, including somatic
chromosomal losses and point mutations, DNA methylation, epigenetic aging, and mitochondrial DNA mutation
and copy number. If successful, this project will provide novel biomarkers of susceptibility and toxicity as well
as biomarkers of the biological effects of arsenic exposure. The biomarkers identified will provide information
useful for (1) identifying subgroups of highly susceptible individuals, (2) understanding biological mechanisms
underlying susceptibility and toxicity, and (3) motivating susceptible individuals to reduce their exposure.
Furthermore, we will continue developing technologies for targeted mea...

## Key facts

- **NIH application ID:** 10896172
- **Project number:** 5R35ES028379-08
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Brandon Lee Pierce
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,211
- **Award type:** 5
- **Project period:** 2017-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896172

## Citation

> US National Institutes of Health, RePORTER application 10896172, Arsenic and the Human Genome:  susceptibility and response to exposure (5R35ES028379-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896172. Licensed CC0.

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