While PDK1 remained significantly associated with ALS risk, no significant association was observed for Cyt-C, and CRAT could not be validated due to limited data, necessitating further investigation.In our MR analysis, the Inverse-Variance Weighted (IVW) method served as the primary analytical approach, supplemented by Weighted Median (WM), MR-Egger, and MR-PRESSO as secondary methods. This evidence concerns the gene PDK1 and amyotrophic lateral sclerosis.