Objective: Observational studies have indicated an association between coffee consumption and amyotrophic lateral sclerosis (ALS). Nevertheless, whether the association is causal is still unclear. We conducted a Mendelian randomization study to explore whether coffee consumption is causally related to ALS. Methods: Two genome-wide association studies (GWASs) investigating coffee consumption (n = 129,422 and 375,833, respectively) were adopted to define instrumental variables for coffee consumption (high vs. infrequent/no, 1 cup/day increase, and 50% increase). Summary-level data for ALS were adopted from a large GWAS of ALS with a total of 20,806 cases and 59,804 controls. Results: Genetically predicted higher coffee consumption was not associated with ALS. The ORs were 1.02 (95% CI: 0.93-1.13; p = 0.649) for high vs. infrequent/no, 0.98 (95% CI: 0.84-1.15; p = 0.822) for 1 cup/day increase, 0.97 (95% CI: 0.79-1.19; p = 0.766) for 50% increase. Sensitivity analyses yielded consistent results. No pleiotropic bias and heterogeneity were observed. Conclusion: Using multiple approaches and sensitivity analyses, our MR results show that genetically predicted coffee consumption was not associated with ALS. Further studies are warranted to explore the effect of coffee consumption on ALS progression.
Keywords: Coffee; Mendelian randomization; amyotrophic lateral sclerosis.