Wang Chengli, Wu Jiayao, Lin Yiqing, Liu Zhongqi, Liufu Ning, Cao Minghui
Department of Anesthesiology, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene, Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Front Neurol. 2024 Jul 17;15:1408956. doi: 10.3389/fneur.2024.1408956. eCollection 2024.
Observational research suggests that hypotension is a potential hazard factor of delirium. Nevertheless, previous observational articles are limited in their ability to establish causality between hypotension and delirium. The present study was sought to explore the genetic causal relationship between these two conditions using two-sample Mendelian randomization (MR).
Genome-wide association study (GWAS) summarized data for hypotension and delirium were obtained from the FinnGen Consortium. The researchers utilized several statistical methods, such as inverse-variance weighted (IVW), weighted median, MR Egger, weighted mode, and simple mode in conducting the MR statistical analysis. In order to identify heterogeneity among the MR outcomes, we employed the Cochrane's Q test. Furthermore, we used the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test to examine horizontal pleiotropy.
The findings revealed that hypotension was identified as an independent hazard variable for delirium ( = 0.010, odds ratio [OR] [95% confidence interval (CI)] = 1.302 [1.066-1.592]) using the IVW method. The presence of horizontal pleiotropy was found to have minimal impact on establishing causal relationship ( = 0.999), and there was no evidence to suggest heterogeneity between genetic variations ( = 0.379). Additionally, the leave-one-out method demonstrated the stability and robustness of this association.
We performed two-sample MR analyses and found evidence of a genetic causal relationship between hypotension and delirium. Our findings suggest that individuals with a genetic predisposition for hypotension may have a higher risk of developing delirium. This suggests that interventions aimed at improving perioperative hypotension could aid in limiting the incidence of delirium.
观察性研究表明，低血压是谵妄的一个潜在危险因素。然而，以往的观察性文章在确定低血压与谵妄之间的因果关系方面能力有限。本研究旨在使用两样本孟德尔随机化（MR）方法探索这两种情况之间的遗传因果关系。
从芬兰基因组联盟获得了低血压和谵妄的全基因组关联研究（GWAS）汇总数据。研究人员在进行MR统计分析时采用了几种统计方法，如逆方差加权（IVW）、加权中位数、MR Egger、加权模式和简单模式。为了确定MR结果之间的异质性，我们采用了Cochrane's Q检验。此外，我们使用MR-Egger截距检验和MR多效性残差总和及异常值（MR-PRESSO）检验来检查水平多效性。
研究结果显示，使用IVW方法，低血压被确定为谵妄的一个独立危险因素（P = 0.010，优势比[OR][95%置信区间（CI）]= 1.302[1.066 - 1.592]）。发现水平多效性的存在对建立因果关系的影响最小（P = 0.999），并且没有证据表明基因变异之间存在异质性（P = 0.379）。此外，留一法证明了这种关联的稳定性和稳健性。
我们进行了两样本MR分析，发现了低血压与谵妄之间存在遗传因果关系的证据。我们的研究结果表明，具有低血压遗传易感性的个体发生谵妄的风险可能更高。这表明旨在改善围手术期低血压的干预措施可能有助于限制谵妄的发生率。
