基于“阳气不足，阴邪弥漫”理论探讨慢性阻塞性肺疾病与脓毒症的关系——基于GWAS数据库的两样本孟德尔随机化研究

Exploring the Relationship between Chronic Obstructive Pulmonary Disease and Sepsis Based on the Theory of “Yang Deficiency and Yin Pathogen Pervasiveness”—A Two-Sample Mendelian Randomization Study Using GWAS Data

摘要: 基于“阳气不足，阴邪弥漫”理论探讨慢性阻塞性肺疾病(COPD)与脓毒症的因果关联。方法：从全基因组关联分析(GWAS)综合统计数据中获取COPD相关遗传位点作为工具变量，脓毒症作为结局，使用两样本孟德尔随机化分析，通过逆方差加权法、MR-Egger回归、简单模型、加权中位数法、加权模型等回归模型OR值和95% CI评估与脓毒症因果关系。使用Cochran’s Q检验评估遗传工具变量异质性，使用MR-Egger截距检验评估多效性，使用“留一法”评估单核苷酸多态性对COPD和脓毒症因果关系影响的敏感性。

Abstract: This study explores the causal relationship between chronic obstructive pulmonary disease (COPD) and sepsis based on the theory of “Yang deficiency and Yin pathogen pervasiveness.” Methods: Genetic loci associated with COPD were obtained from genome-wide association study (GWAS) summary statistics as instrumental variables, with sepsis as the outcome. A two-sample Mendelian randomization analysis was conducted using inverse variance weighting (IVW), MR-Egger regression, simple model, weighted median, and weighted mode regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the causal association with sepsis. Cochran’s Q test was applied to assess heterogeneity among genetic instruments, MR-Egger intercept test was used to evaluate pleiotropy, and a “leave-one-out” sensitivity analysis was performed to assess the influence of individual single nucleotide polymorphisms (SNPs) on the causal relationship between COPD and sepsis.