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

Introduction: Environmental exposures strongly influence ALS risk and identification is needed to reduce ALS burden. Participation in hobbies and exercise may alter ALS risk and phenotype, warranting an assessment to understand their contribution to the ALS exposome. Methods: Participants with ALS and healthy controls were recruited from University of Michigan and self-completed a survey to ascertain hobbies, exercise, and avocational exposures. Exposure variables were associated with ALS risk, survival, onset segment, and onset age. Results: ALS (n = 400) and control (n = 287) participants self-reported avocational activities. Cases were slightly older (median age 63.0 vs. 61.1 years, p = 0.019) and had a lower educational attainment (p < 0.001) compared to controls; otherwise, demographics were well balanced. Risks associating with ALS after multiple comparison correction included golfing (odds ratio (OR) 3.48, p(adjusted) = 0.004), recreational dancing (OR 2.00, p(adjusted) = 0.040), performing gardening or yard work (OR 1.71, p(adjusted) = 0.040) five years prior to ALS and personal (OR 1.76, p(adjusted) = 0.047) or family (OR 2.21, p(adjusted) = 0.040) participation in woodworking, and personal participation in hunting and shooting (OR 1.89, p(adjusted) = 0.040). No exposures associated with ALS survival and onset. Those reporting swimming (3.86 years, p(adjusted) = 0.016) and weightlifting (3.83 years, p(adjusted) = 0.020) exercise 5 years prior to ALS onset had an earlier onset age. Discussion: The identified exposures in this study may represent important modifiable ALS factors that influence ALS phenotype. Thus, exposures related to hobbies and exercise should be captured in studies examining the ALS exposome.