Department of Neurology, Peking University Third Hospital, Garden North Road No. 49, Beijing, 100191, China.
Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China.
Orphanet J Rare Dis. 2022 Feb 16;17(1):56. doi: 10.1186/s13023-022-02212-0.
Observational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. The authors employed a bidirectional two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between BP and ALS. Genetic proxies for systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs (AHDs), ALS, and their corresponding genome-wide association study (GWAS) summary datasets were obtained from the most recent studies with the largest sample sizes. The inverse variance weighted (IVW) method was adopted as the main approach to examine the effect of BP on ALS and four other MR methods were used for sensitivity analyses. To exclude the interference between SBP and DBP, a multivariable MR approach was used.
We found that genetically determined increased DBP was a protective factor for ALS (OR = 0.978, 95% CI 0.960-0.996, P = 0.017) and that increased SBP was an independent risk factor for ALS (OR = 1.014, 95% CI 1.003-1.025, P = 0.015), which is supported by sensitivity analyses. The use of calcium channel blocker (CCB) showed a causal relationship with ALS (OR = 0.985, 95% CI 0.971-1.000, P = 0.049). No evidence was revealed that ALS caused changes in BP.
This study provides genetic support for a causal effect of BP and ALS that increased DBP has a protective effect on ALS, and increased SBP is a risk factor for ALS, which may be related to sympathetic excitability. Blood pressure management is essential in ALS, and CCB may be a promising candidate.
观察性研究表明，血压（BP）与肌萎缩侧索硬化症（ALS）之间存在密切但有争议的关系。目前尚不清楚这种关联是否具有因果关系。作者采用双向两样本孟德尔随机化（MR）方法来评估 BP 与 ALS 之间的因果关系。从最近具有最大样本量的研究中获得了收缩压（SBP）、舒张压（DBP）、降压药物（AHDs）、ALS 的遗传替代物及其相应的全基因组关联研究（GWAS）汇总数据集。采用逆方差加权（IVW）方法作为主要方法来检验 BP 对 ALS 的影响，同时还使用了另外四种 MR 方法进行敏感性分析。为了排除 SBP 和 DBP 之间的干扰，采用了多变量 MR 方法。
我们发现，遗传上确定的 DBP 升高是 ALS 的保护因素（OR=0.978，95%CI 0.960-0.996，P=0.017），而 SBP 升高是 ALS 的独立危险因素（OR=1.014，95%CI 1.003-1.025，P=0.015），这些结果在敏感性分析中得到了支持。钙通道阻滞剂（CCB）的使用与 ALS 呈因果关系（OR=0.985，95%CI 0.971-1.000，P=0.049）。没有证据表明 ALS 导致 BP 变化。
本研究为 BP 和 ALS 之间存在因果关系提供了遗传证据，即 DBP 升高对 ALS 有保护作用，SBP 升高是 ALS 的危险因素，这可能与交感神经兴奋性有关。在 ALS 中，血压管理至关重要，CCB 可能是一种有前途的候选药物。
