数字中医药（英文）2025，Vol.8Issue(2)：196-205,10.DOI:10.1016/j.dcmed.2025.05.003
基于孟德尔随机化和中医情志学说阐明不良情绪诱导慢性阻塞性肺疾病产生机制
Validating the pathogenic mechanism of chronic obstructive pulmonary disease induced by negative emotions via Mendelian randomization and traditional Chinese medicine theory of emotions
摘要
Abstract
Objective We employed Mendelian randomization(MR)to test the traditional Chinese medicine(TCM)theory of emotional pathogenesis concept and explore the causal relation-ship between negative emotions and chronic obstructive pulmonary disease(COPD). Methods Data of negative emotions,bronchitis,emphysema,and C-reactive protein(CRP)levels were downloaded from genome-wide association study(GWAS)public database for a two-sample MR analysis.Independent single-nucleotide polymorphisms(SNPs)associated with negative emotions,bronchitis,and emphysema were selected as instrumental variables.Primary causal estimates were derived using inverse-variance weighting(IVW),supplement-ed by weighted median(WM),and simple mode(SM)methods.Sensitivity analyses included MR-Egger regression and MR-PRESSO to assess pleiotropy,Cochran's Q test for heterogene-ity,and multivariate MR to adjust for smoking.Mediation analysis evaluated the role of in-flammatory markers.Reverse MR was tested for bidirectional causality.Weak instrument bias was mitigated via F-statistic thresholds(>10).All analyses were conducted in RStudio. Results MR analysis identified significant causal effects of several negative emotions on COPD.Genetically,the IVW analysis of seen doctors for nerves anxiety tension or depression[ORIVW=1.006,95%CI=(1.002,1.010),P=0.002],sensitivity/hurt feelings[ORIVW=1.024,95%CI=(1.004,1.044),P=0.017],and irritability[ORIVW=1.019,95%CI=(1.003,1.035),P=0.019 were robustly associated with increased risks of COPD.No heterogeneity was detected among the different instrumental variables(IVs)for depression(P=0.655)and irritability(P=0.163).MR-Egger regression intercepts for all emotional exposures were close to zero and sta-tistically non-significant,indicating no evidence of directional pleiotropy.The horizontal pleiotropy results showed that except for worry(MR-PRESSO P=0.006),other emotion expo-sures confirming no substantial pleiotropic bias.Multivariable MR demonstrated that anxiety remained independently associated with COPD after adjusting for smoking(P=0.002),while associations with other negative emotions were attenuated post-adjustment.The mediation analysis revealed that CRP mediated 3.93%of the total effect of anxiety on COPD.However,reverse MR analysis found no evidence of reverse causality. Conclusion This study confirmed the causal effects of negative emotions on COPD through MR analysis and revealed that negative emotions may trigger CRP production,which plays an essential mediating role in this relationship.This study provides a reliable modern theoreti-cal basis for emotion theory in TCM.关键词
中医/情志致病/孟德尔随机化/逆方差加权法/慢性阻塞性肺疾病Key words
Traditional Chinese medicine(TCM)/Emotion-induced pathogenesis/Mendelian randomization/Inverse-variance weighting/Chronic obstructive pulmonary disease(COPD)引用本文复制引用
王治英,李芸,钟治贤,许玲,钟薏,陈健..基于孟德尔随机化和中医情志学说阐明不良情绪诱导慢性阻塞性肺疾病产生机制[J].数字中医药（英文）,2025,8(2):196-205,10.基金项目
2024 National"Flagship"Department Construction Project of Traditional Chinese and Western Medicine Co-operation,Shandong Province Rural Revitalization Foun-dation Xiulan ZHANG Charity Fund,and Key Discipline of Shanghai Health System in 2024(2024ZDXK0026). （2024ZDXK0026）
