既往研究强调肺癌（LC）与脓毒症之间的相关性，但其因果关系仍不清楚。本研究采用单变量孟德尔随机化（MR）来探讨LC及其亚型与脓毒症之间的因果关系。使用连锁不平衡评分（LDSC）回归来计算遗传相关性。应用多变量 MR 来研究七个混杂因素的作用。使用的主要方法是逆方差加权 (IVW)，并辅以敏感性分析来评估方向性、异质性和结果稳健性。LDSC 分析显示 LC 和脓毒症之间存在显着的遗传相关性（遗传相关性 = 0.325，p = 0.014）。经过错误发现率 (FDR) 校正后，强有力的证据表明基因预测的 LC（OR = 1.172，95% CI 1.083-1.269，p = 8.29 × 10-5，P fdr = 2.49 × 10-4），鳞状细胞肺癌（OR = 1.098，95% CI 1.021-1.181，p = 0.012，P fdr = 0.012）和肺腺癌（OR = 1.098，95% CI 1.024-1.178，p = 0.009，P fdr = 0.012）与败血症的发生率增加。还发现小细胞肺癌（Wald 比：OR = 1.156，95% CI 1.047-1.277，p = 0.004）与脓毒症相关的提示性证据。多变量 MR 表明所有 LC 亚型对脓毒症的部分影响可能是通过体重指数介导的。反向分析未发现因果关系（p > 0.05 且 P fdr > 0.05）。该研究表明 LC 与脓毒症风险增加之间存在因果关系，强调了 LC 患者进行综合脓毒症管理的必要性。版权所有 © 2024 Zhou，Zhang，杨、张、李、李、彭、陈。

Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear.This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness.LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, p = 8.29 × 10-5, P fdr = 2.49 × 10-4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, p = 0.012, P fdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, p = 0.009, P fdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p > 0.05 and P fdr > 0.05).The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients.Copyright © 2024 Zhou, Zhang, Yang, Zhang, Li, Li, Peng and Chen.