Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis.

Background:  Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable.

Objective:  To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis.

Methods:  The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method.

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). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS.

Conclusion:  In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.