Results We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001–1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956–0.984;p = 1.96 × 10−5; per 10-mmHg decrement). The gene discussed is ACE; the disease is amyotrophic lateral sclerosis.