赖诺普利与肺炎的关系：基于GWAS两样本 孟德尔随机化研究

The Relationship between Lisinopril and Pneumonia: A Two-Sample Mendelian Randomization Study Based on GWAS Data

摘要: 目的：探讨赖诺普利与肺炎发生之间的因果关系。方法：从全基因组关联分析(GWAS)综合统计数据中筛选出58个与赖诺普利相关的遗传位点作为工具变量，以肺炎作为结局，采用两样本孟德尔随机化(MR)分析。通过逆方差加权法(IVW)、MR-Egger回归、简单模型(Simple Mode)、加权中位数法(Weighted Median)、加权模型(Weighted Mode)等回归模型，计算OR值和95%置信区间(CI)，评估赖诺普利与肺炎之间的因果关系。同时，使用Cochran’s Q检验评估遗传工具变量的异质性，MR-Egger截距检验检测是否存在多效性，并以“留一法”评估单核苷酸多态性(SNPs)对赖诺普利和肺炎因果关系影响的敏感性。结果：IVW分析结果显示，赖诺普利使用与肺炎风险呈负相关(p = 0.002)；Weighted Median分析结果也支持二者存在因果关系，OR值和95% CI为0.93 (0.89~0.98, p = 0.011)，其他回归模型未达到统计学显著性(p > 0.05)。异质性检验表明该关联具有异质性，多效性检验未发现明显的水平多效性问题。“留一法”分析表明结果具有稳健性。结论：本研究证实赖诺普利对肺炎的发生具有一定的保护作用，为其在临床实践中的潜在益处提供了新的视角。

Abstract: Objective: To investigate the causal relationship between lisinopril use and the occurrence of pneumonia. Methods: A total of 58 genetic variants associated with lisinopril were selected as instrumental variables from the summary statistics of genome-wide association studies (GWAS). Pneumonia was defined as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using multiple regression models, including inverse variance weighted (IVW), MR-Egger regression, simple mode, weighted median, and weighted mode approaches. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the causal effect of lisinopril on pneumonia. Heterogeneity among instrumental variables was evaluated using Cochran’s Q test, horizontal pleiotropy was examined with the MR-Egger intercept test, and the “leave-one-out” sensitivity analysis was conducted to assess the robustness of the results. Results: The IVW analysis indicated a negative association between lisinopril use and the risk of pneumonia (p = 0.002). The weighted median method also supported a causal relationship between lisinopril and pneumonia, with an OR (95% CI) of 0.93 (0.89~0.98, p = 0.011). Other regression models did not reach statistical significance (p > 0.05). Heterogeneity testing revealed the presence of heterogeneity, while no substantial horizontal pleiotropy was detected. The “leave-one-out” analysis confirmed the robustness of the findings. Conclusion: This study provides evidence that lisinopril may exert a protective effect against the development of pneumonia, offering new insights into its potential clinical benefits.