ALS risk factors: Industrial airborne chemical releases

Angeline Andrew*, Jie Zhou, Jiang Gui, Xun Shi, Meifang Li, Antoinette Harrison, Bart Guetti, Ramaa Nathan, Tanya Butt, Daniel Peipert, Maeve Tischbein, Erik P. Pioro, Elijah Stommel, Walter Bradley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Most amyotrophic lateral sclerosis (ALS) cases are sporadic (∼90%) and environmental exposures are implicated in their etiology. Large industrial facilities are permitted the airborne release of certain chemicals with hazardous properties and report the amounts to the US Environmental Protection Agency (EPA) as part of its Toxics Release Inventory (TRI) monitoring program. The objective of this project was to identify industrial chemicals released into the air that may be associated with ALS etiology. We geospatially estimated residential exposure to contaminants using a de-identified medical claims database, the SYMPHONY Integrated Dataverse®, with ∼26,000 nationally distributed ALS patients, and non-ALS controls matched for age and gender. We mapped TRI data on industrial releases of 523 airborne contaminants to estimate local residential exposure and used a dynamic categorization algorithm to solve the problem of zero-inflation in the dataset. In an independent validation study, we used residential histories to estimate exposure in each year prior to diagnosis. Air releases with positive associations in both the SYMPHONY analysis and the spatio-temporal validation study included styrene (false discovery rate (FDR) 5.4e-5), chromium (FDR 2.4e-4), nickel (FDR 1.6e-3), and dichloromethane (FDR 4.8e-4). Using a large de-identified healthcare claims dataset, we identified geospatial environmental contaminants associated with ALS. The analytic pipeline used may be applied to other diseases and identify novel targets for exposure mitigation. Our results support the future evaluation of these environmental chemicals as potential etiologic contributors to sporadic ALS risk.

Original languageEnglish (US)
Article number118658
JournalEnvironmental Pollution
StatePublished - Feb 15 2022


  • Airborne
  • Amyotrophic lateral sclerosis
  • Residential history
  • Risk factors
  • Solvents

ASJC Scopus subject areas

  • Toxicology
  • Pollution
  • Health, Toxicology and Mutagenesis


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