# Identify, Analyze, and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS) - 2018

> **NIH ALLCDC R01** · DARTMOUTH-HITCHCOCK CLINIC · 2020 · $500,000

## Abstract

ABSTRACT
ALS is a devastating and fatal neurodegenerative disease for which there is no cure or effective treatment. The
causes of ALS likely involve interaction of environmental and genetic susceptibility factors. Exposure to the
damaging environmental stressors likely occurs at particularly susceptible time-periods, and for a prolonged
period. We will investigate the époques during which environmental exposures carry the greatest risk for later
development of ALS. We will use questionnaire data, residential history, and DNA samples from our on-going
epidemiologic studies in Northern New England and Ohio, the existing environmental and genetic variant data
from the National ALS Registry for ALS patients nationwide, and both clinic- and random population-based
controls. We will use geospatial algorithms to estimate residential exposures in years extending backwards for
~30 years derived from our databases of time-linked contents of sources of environmental toxins (cyanobacteria)
and toxicants (landfills, municipal incinerators, Superfund and Brownfield sites, pesticide applications). We also
propose to identify genetic risk factors for ALS that manifest effects specifically in the presence of an
environmental stressor. We will use the existing Illumina NeuroChip data covering 500,000 genetic variants
implicated in neurodegenerative illness on the National ALS Biorepository participants, and propose to assay
our epidemiologic study DNA samples on the same panel to construct a large, pooled genotype dataset. Genetic
imputation will allow genome-wide coverage for identification of novel variants. We will employ the machine-
learning methods to identify gene x environment interactions, the genetic variants that synergize with
environmental stressors to increase disease risk. This project has the potential to identify the environmental and
genetic risk factors in periods of temporal susceptibility that will lead to disease prevention through exposure
mitigation, early-identification, and development of interventions to block disease progression.

## Key facts

- **NIH application ID:** 9973035
- **Project number:** 5R01TS000288-03
- **Recipient organization:** DARTMOUTH-HITCHCOCK CLINIC
- **Principal Investigator:** Erik Paul Pioro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2020
- **Award amount:** $500,000
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973035

## Citation

> US National Institutes of Health, RePORTER application 9973035, Identify, Analyze, and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS) - 2018 (5R01TS000288-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973035. Licensed CC0.

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