Validating the pathogenic mechanism of chronic obstructive pulmonary disease induced by negative emotions via Mendelian randomization and traditional Chinese medicine theory of emotions
10.1016/j.dcmed.2025.05.003
- VernacularTitle: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
- Author:
Zhiying WANG
;
Yun LI
;
Zhixian ZHONG
;
Ling XU
;
Yi ZHONG
;
Jian CHEN
- Publication Type:Journal Article
- Keywords:
Traditional Chinese medicine (TCM);
Emotion-induced pathogenesis;
Mendelian randomization;
Inverse-variance weighting;
Chronic obstructive pulmonary disease (COPD)
- From:
Digital Chinese Medicine
2025;8(2):196-205
- CountryChina
- Language:English
-
Abstract:
Objective:We employed Mendelian randomization (MR) to test the traditional Chinese medicine (TCM) theory of emotional pathogenesis concept and explore the causal relationship 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), supplemented 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 heterogeneity, and multivariate MR to adjust for smoking. Mediation analysis evaluated the role of inflammatory 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 statistically non-significant, indicating no evidence of directional pleiotropy. The horizontal pleiotropy results showed that except for worry (MR-PRESSO P = 0.006), other emotion exposures 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 theoretical basis for emotion theory in TCM.
- Full text:2025071323013035731wangzhiying.pdf
