# Epigenetic and genetic regulation of arsenic methylation and arsenic-relatedcardiovascular disease risk

> **NIH NIH K99** · STANFORD UNIVERSITY · 2024 · $125,847

## Abstract

SUMMARY
In the United States, Native American communities face the greatest burden of chronic diseases among all ethnic
groups and high rates of cardiovascular disease (CVD) incidence and mortality. Elevated disease risk may be in
part attributed to arsenic in drinking water, which is a key environmental risk factor among rural households that
rely on private wells. Arsenic-related CVD risk may be modified by the biomethylation of arsenic, a pathway that
decreases arsenic toxicity and increases urinary excretion. Arsenic methylation efficiency varies between
individuals and populations and is influenced by genetic variation. However, the role of pre- and post-
transcriptional gene regulatory factors, including DNA methylation (DNAm) and microRNAs, on arsenic
methylation efficiency and arsenic-induced CVD is not fully understood. This study will leverage data and
biospecimens representing multiple omics layers from the Strong Heart Study (SHS) and Strong Heart Family
Study (SHFS), large, prospective, well characterized cohorts of Native American adults with longitudinal data on
CVD outcomes and risk biomarkers. The aims of this project are to (K00, Aim 1) determine the relationship
between DNAm, arsenic methylation efficiency, and CVD to identify epigenetic biomarkers of arsenic toxicity and
arsenic-related disease risk; (K99, Aim 2) determine the effect of genetic variation on DNAm associated with
arsenic methylation efficiency to distinguish molecular mechanisms underlying arsenic methylation phenotypes;
and (R00, Aim 3) investigate the role of microRNAs in mediating the association between arsenic exposure and
methylation efficiency and CVD risk biomarkers to elucidate molecular processes underlying arsenic-related
CVD. To accomplish these aims, Dr. Bozack will be receive mentorship from experts in environmental, molecular,
and genetic epidemiology. In the K99 phase, Dr. Bozack will also receive training in bioinformatics and machine
learning, including approaches for developing DNAm biomarkers and investigating gene-epigene interactions.
In the R00 phase, she will generate circulating microRNA expression data and will further apply her training in
clustering and network analyses to identify microRNA signatures linking arsenic exposure and methylation
efficiency to CVD risk. The proposed training and research will enable Dr. Bozack to establish an independent
research path focusing on biomarker development and applying multiple omics approaches to environmental
molecular epidemiology. Furthermore, mentorship and career development activities will facilitate her transition
to an independent researcher. Overall, this study will advance the understanding of gene regulatory factors
involved in arsenic-related CVD risk through a multiple omics perspective, which is necessary to unravel the
relationship between environmental and biological factors involved in the etiology of complex diseases. Findings
will contribute the development of noninvasive bi...

## Key facts

- **NIH application ID:** 10807890
- **Project number:** 1K99ES035109-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Anne Kristina Bozack
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $125,847
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807890

## Citation

> US National Institutes of Health, RePORTER application 10807890, Epigenetic and genetic regulation of arsenic methylation and arsenic-relatedcardiovascular disease risk (1K99ES035109-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10807890. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*