肺癌与败血症之间的因果关系：遗传相关性和多元孟德尔随机分析
Causal relationships between lung cancer and sepsis: a genetic correlation and multivariate mendelian randomization analysis
影响因子:2.80000
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
摘要
以前的研究强调了肺癌（LC）和败血症之间存在相关性，但因果关系仍然不清楚。这项研究使用单变量的孟德尔随机化（MR）来探索LC，其亚型和败血症之间的因果关系。连锁不平衡评分（LDSC）回归用于计算遗传相关性。多变量MR用于研究七个混杂因素的作用。所使用的主要方法是反相关加权（IVW），并通过灵敏度分析来评估方向性，异质性和鲁棒性。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）。遵循错误的发现率（FDR）校正，有力的证据表明，遗传预测的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 1.01 p = 0.01 p.1dr = 0.01 pr = 0.01 ci fdre 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有关。还发现了针对小细胞肺癌（WALD比：OR = 1.156，95％CI 1.047-1.277，p = 0.004）的暗示性证据。多变量MR建议所有LC亚型对败血症的部分影响可能通过体重指数介导。反向分析没有发现因果关系（p> 0.05和p fdr> 0.05）。这项研究表明，LC与增加的败血症风险之间存在致病联系，强调了LC患者综合败血症的需求。
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.