# RFA-TS-23-001: Establishing the Cohort for Occupational Risk and Prevention Studies for Amyotrophic Lateral Sclerosis (ALS CORPS)

> **NIH ALLCDC R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $500,000

## Abstract

ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal motor neuron disease that likely results from a
combination of lifetime non-genetic exposures—defined as the ALS exposome—and underlying genetic risk.
Through ALS case-control studies, we identified that workers in Production Occupations and with occupational
metal exposures carry a higher ALS risk; thus, we are interested in understanding how these occupational
exposures and the exposome interact with genetics to inform ALS prevention efforts. In response to RFA-TS-
23-001 Funding Option A, we will address this need by establishing a longitudinal cohort of individuals at
higher ALS risk, enriched by occupation and occupational metal exposure, to facilitate ALS gene and
exposome studies. In this prospective longitudinal cohort of at-risk individuals, we will monitor the ALS
exposome, polygenic risk, and phenoconversion in real time. Our overall objective is to identify cumulative risk
factors that contribute to ALS phenoconversion. Our central hypothesis is that the ALS exposome and
underlying genetic risk contribute to disease phenoconversion and provide targets for ALS prevention. We are
guided by preliminary data showing that: i) work in Production Occupations and occupational metal exposure
strongly associate with ALS risk, ii) factors beyond occupational exposures also contribute to ALS risk, and iii)
genetic architecture by polygenic risk contributes to ALS risk. Our rationale is that a prospective cohort will
enable ascertainment of critical exposure windows or exposure interactions, which can be targeted to prevent
ALS phenoconversion in persons at higher risk. We will test the central hypothesis via three aims. In Aim 1, we
will establish a prospective, longitudinal cohort of 5,000 individuals with higher ALS risk based on established
occupational risk factors by recruiting via targeted online postings. In Aim 2, we will use our detailed exposure
assessment tools to ascertain occupational, residential, avocational, and lifestyle exposures (ALS exposome)
which cumulatively contribute to ALS risk. We will also obtain early indicators of phenoconversion for all
participants, including body mass index and mild motor and cognitive impairment, to establish the cohort’s
exposure risks and phenoconversion indices at baseline, thereby allowing for future critical research on ALS
risk and prevention. Finally, in Aim 3, we will determine the polygenic risk of ALS in the cohort by genotyping
buccal DNA from participants to establish the baseline genetic risk to integrate with the ALS exposome. The
proposed research is highly significant because we expect to (1) establish a first in kind, non-familial but at-risk
ALS cohort with detailed baseline exposome phenotyping and assessment of phenoconversion markers and
(2) assess polygenic risk to further stratify ALS risk. Longitudinal follow-up will identify the critical time windows
when interventions can modify disease onset. This is a...

## Key facts

- **NIH application ID:** 10909768
- **Project number:** 5R01TS000344-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Eva Lucille Feldman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2024
- **Award amount:** $500,000
- **Award type:** 5
- **Project period:** 2023-09-30 → 2026-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909768

## Citation

> US National Institutes of Health, RePORTER application 10909768, RFA-TS-23-001: Establishing the Cohort for Occupational Risk and Prevention Studies for Amyotrophic Lateral Sclerosis (ALS CORPS) (5R01TS000344-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909768. Licensed CC0.

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