# Health Effects of Metals in Native American Communities: A Longitudinal Multi-omics Study

> **NIH NIH P42** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $494,135

## Abstract

Summary of Project 3
Native American populations have higher rates of cardiometabolic disease, including cardiovascular disease
(CVD) and diabetes, than any other racial/ethnic group in the US. In the Strong Heart Study (SHS), the most
important study of CVD and its risk factors in Native American communities, we showed that long-term arsenic
(As) exposure can explain part of the excess burden of cardiometabolic disease. Uranium (U) exposure is
associated with CVD in occupational cohorts, but data from general populations are limited. Importantly, As and
U are common contaminants in Superfund sites and tribal lands, so exposure to these contaminants could be
partially responsible for increased rates of cardiometabolic disease in Native American populations. Advancing
effective interventions for metal-related cardiometabolic diseases requires robust data on the lasting effects of
past exposures, the joint effects of As and U, and the relevant mechanisms, including downstream molecular
effects. To address these needs, we will establish the Strong Heart As/U Lifelong (SHAUL) study (n=1,300) by
linking data from participants at SHS visit 1 (1989–91) with their offspring recruited during the SHS family
expansion in 2001–03 (visit 4). We will leverage 30 years of data and a new visit planned for 2022–23 to address
the following aims. (1) Determine the cardiometabolic effects (diabetes and CVD) of childhood and adult
As and U exposures overall and by sex, region, and nutritional status. Urinary metal biomarkers are available
at visits 1 (reflecting childhood exposure) and 4 (reflecting adult exposure), and will be measured at visits 5
(2006–09) and 7 (2022–23) to reconstruct lifelong exposures. Water metal data, including spatial patterns,
temporal trends, and stable isotope data tracing potential sources, will be available from Projects 1 and 2. (2)
Determine the longitudinal epigenetic and metabolomic effects of childhood and adult As and U
exposures overall and by sex, region, and nutritional status. We will measure genome-wide DNA methylation
(DNAm) at visits 4 and 5, leverage extant targeted and untargeted metabolomics from the same visits, and use
a joint DNAm/metabolomic multi-omics strategy. (3) Develop a predictive multi-omics fingerprint that
quantifies latent and concurrent cardiometabolic risk due to As and U exposures. We will use machine
learning approaches to characterize DNAm and metabolomic profiles that identify individuals at risk of diabetes
or CVD due to past or current metal exposures. We will also conduct a cross-species multi-omics comparison
with Project 4’s mouse data. Cardiovascular disease, diabetes, and metal exposures are major concerns for our
partnering communities in the Northern Plains. By investigating the latent and concurrent effects of As and U
exposures, the SHAUL study can reveal epigenetic and metabolomic mechanisms for metal-induced health
effects, identify susceptible populations, and inform risk assessment. Th...

## Key facts

- **NIH application ID:** 10354271
- **Project number:** 1P42ES033719-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ana Navas-Acien
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,135
- **Award type:** 1
- **Project period:** 2022-09-21 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354271

## Citation

> US National Institutes of Health, RePORTER application 10354271, Health Effects of Metals in Native American Communities: A Longitudinal Multi-omics Study (1P42ES033719-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10354271. Licensed CC0.

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