Alcohol Drinking and Amyotrophic Lateral Sclerosis: An Instrumental Variable Causal Inference.

Observational studies have shown alcohol drinking behaviors may be associated with the risk of amyotrophic lateral sclerosis (ALS), but contradictory findings have emerged, and whether such an association is causal is unclear. We here investigate the causal relationship between alcohol consumption and ALS. By leveraging instruments from large-scale genome-wide association studies, we performed a comprehensive Mendelian randomization analysis and found alcohol consumption was causally associated with ALS, leading to ∼1.5-fold (95% confidence interval = 1.4-3.4) higher risk of ALS for each ∼10g/day increase in alcohol intake. Our findings suggest accumulative alcohol consumption may serve as a crucial risk factor in the pathogenesis of ALS. ANN NEUROL 2020 ANN NEUROL 2020;88:195-198.