Residential exposure associations with ALS risk, survival, and phenotype: a Michigan-based case-control study

Abstract

Background: Environmental exposures impact amyotrophic lateral sclerosis (ALS) risk and progression, a fatal and progressive neurodegenerative disease. Better characterization of these exposures is needed to decrease disease burden. Objective: To identify exposures in the residential setting that associate with ALS risk, survival, and onset segment. Methods: ALS and control participants recruited from University of Michigan completed a survey that ascertained exposure risks in the residential setting. ALS risk was assessed using logistic regression models followed by latent profile analysis to consider exposure profiles. A case-only analysis considered the contribution of the residential exposure variables via a Cox proportional hazards model for survival outcomes and multinomial logistic regression for onset segment, a polytomous outcome. Results: This study included 367 ALS and 255 control participants. Twelve residential variables were associated with ALS risk after correcting for multiple comparison testing, with storage in an attached garage of chemical products including gasoline or kerosene (odds ratio (OR) = 1.14, p_adjusted < 0.001), gasoline-powered equipment (OR = 1.16, p_adjusted < 0.001), and lawn care products (OR = 1.15, p_adjusted < 0.001) representing the top three risk factors sorted by p_adjusted. Latent profile analysis indicated that storage of these chemical products in both attached and detached garages increased ALS risk. Although residential variables were not associated with poorer ALS survival following multiple testing corrections, storing pesticides, lawn care products, and woodworking supplies in the home were associated with shorter ALS survival using nominal p values. No exposures were associated with ALS onset segment. Conclusion: Residential exposures may be important modifiable components of the ALS susceptibility and prognosis exposome.

Keywords:

• ALS
• residential risk factors
• ALS exposures
• pesticides
• woodworking
• gasoline
• lawn care products

Acknowledgements

We are indebted to the study participants that provided information. We thank Blake Swihart, Adam Patterson, Jayna Duell, RN, Daniel Berger, Amanda Williams, and Scott Dent for study support. We also thank Dr. Emily J. Koubek for expert editorial assistance.

Author contributions

SAG: drafting/revising the manuscript for content, study concept and design, analysis and interpretation of data. JB: drafting/revising the manuscript for content, analysis, and interpretation of data. DGJ: drafting/revising the manuscript for content, analysis, and interpretation of data. CP: drafting/revising the manuscript for content, data collection. HF: drafting/revising the manuscript for content, data collection. MB: drafting/revising the manuscript for content, data collection. BM: analysis and interpretation of data, drafting/revising the manuscript for content. ELF: drafting/revising the manuscript for content, study concept and design, analysis and interpretation of data. SAB: drafting/revising the manuscript for content, study concept and design, analysis and interpretation of data.

Declaration of interest

SAG and ELF are listed as inventors on a patent, Issue number US10660895, held by the University of Michigan titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics. All other authors have nothing to disclose.

Data availability statement

Sharing of non-identifiable data will be considered at the reasonable request of a qualified investigator.

Additional information

Funding

This work was supported by the National Institutes of Health (K23ES027221; R01ES030049; R01NS127188), National ALS Registry/CDC/ATSDR (CDC/ATSDR 200-2013-56856), the NeuroNetwork for Emerging Therapies, the Robert and Katherine Jacobs Environmental Health Initiative, the NeuroNetwork Therapeutic Discovery Fund, the Peter R. Clark Fund for ALS Research, the Sinai Medical Staff Foundation, Scott L. Pranger, the University of Michigan; National Center for Advancing Translational Sciences at the National Institutes of Health (UL1TR002240).