肺癌与败血症之间的因果关系：遗传相关性与多变量孟德尔随机分析

Causal relationships between lung cancer and sepsis: a genetic correlation and multivariate mendelian randomization analysis

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Frontiers in Genetics

影响因子:2.8

分区:生物学3区 / 遗传学3区

发表日期:2024

作者: Jiejun Zhou, Youqian Zhang, Tian Yang, Kun Zhang, Anqi Li, Meng Li, Xiaojing Peng, Mingwei Chen

DOI: 10.3389/fgene.2024.1381303

摘要

以往研究强调肺癌（LC）与败血症之间存在相关性，但其因果关系仍不明确。本研究采用单变量孟德尔随机（MR）方法探讨肺癌及其亚型与败血症的因果关系。使用连锁不平衡评分（LDSC）回归计算遗传相关性。多变量MR用于研究七个混杂因素的作用。主要采用逆方差加权（IVW）方法，并通过敏感性分析评估方向性、异质性和结果的稳健性。LDSC分析显示，肺癌与败血症之间存在显著的遗传相关性（遗传相关性=0.325，p=0.014）。经过FDR校正后，强有力的证据表明，遗传预测的肺癌（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）及腺癌（OR=1.098，95%CI 1.024-1.178，p=0.009，P_fdr=0.012）与败血症发生率增加相关。还发现小细胞肺癌（Wald比：OR=1.156，95%CI 1.047-1.277，p=0.004）与败血症有关的迹象。多变量MR分析提示，所有肺癌亚型对败血症的部分影响可能通过身体质量指数（BMI）中介。逆向分析未发现因果关系（p>0.05，P_fdr>0.05）。研究表明肺癌与败血症风险增加之间存在因果联系，强调了在肺癌患者中实施综合败血症管理的必要性。

Abstract

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.