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 obstruc...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[OR_(IVW)=1.006,95%CI=(1.002,1.010),P=0.002],sensitivity/hurt feelings[OR_(IVW)=1.024,95%CI=(1.004,1.044),P=0.017],and irritability[OR_(IVW)=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 theoretical basis for emotion theory in TCM.展开更多
Background and Objectives:This study aims to examine the causal relationship between dietary factors and ulcerative colitis(UC).Methods and Study Design:The analysis utilized data from genome-wide association studies(...Background and Objectives:This study aims to examine the causal relationship between dietary factors and ulcerative colitis(UC).Methods and Study Design:The analysis utilized data from genome-wide association studies(GWAS).Dried fruit,vegetables,processed meat,fresh fruit,and cereal intake were examined as exposure factors.UC was considered the outcome.Two-sample Mendelian randomization(TSMR)analysis was performed using methods.Heterogeneity and horizontal pleiotropy assessments were conducted to ensure the robustness of our findings.Additionally,we applied False Discovery Rate(FDR)corrections for multiple tests.Results:The analysis revealed a significant inverse causal relationship between dried fruit intake and UC risk(odds ratio[OR]:0.488,95%confidence interval[CI]:0.261 to 0.915,p=0.025).No significant association was observed between vegetable intake(OR:1.742,95%CI:0.561 to 5.415,p=0.337),processed meat intake(OR:1.136,95%CI:0.552 to 2.339,p=0.729),fresh fruit intake(OR:0.977,95%CI:0.465 to 2.054,p=0.952),cereal intake(OR:1.195,95%CI:0.669 to 2.134,p=0.547).The low heterogeneity observed across analyses and the confirmation of stability through leave-one-out analysis reinforce the reliability of these results.Moreover,after adjusting for multiple tests,none of the dietary factors reached a p-value below the conventional significance threshold of 0.05.Conclusions:This study provides evidence of a potential association between dried fruit intake and a reduced risk of UC.Further MR studies incorporating larger GWAS datasets are needed to confirm these findings.展开更多
基金2024 National “Flagship” Department Construction Project of Traditional Chinese and Western Medicine CooperationShandong Province Rural Revitalization Foundation Xiulan ZHANG Charity FundKey Discipline of Shanghai Health System in 2024 (2024ZDXK0026)。
文摘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[OR_(IVW)=1.006,95%CI=(1.002,1.010),P=0.002],sensitivity/hurt feelings[OR_(IVW)=1.024,95%CI=(1.004,1.044),P=0.017],and irritability[OR_(IVW)=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 theoretical basis for emotion theory in TCM.
基金funded by the Beijing University of Chinese Medicine Academic Leader Support Plan(90010960920033)but also by the high-level Traditional Chinese Medicine key subjects construction project of the National Administration of Traditional Chinese Medicine——Evidencebased Traditional Chinese Medicine(zyyzdxk-2023249).
文摘Background and Objectives:This study aims to examine the causal relationship between dietary factors and ulcerative colitis(UC).Methods and Study Design:The analysis utilized data from genome-wide association studies(GWAS).Dried fruit,vegetables,processed meat,fresh fruit,and cereal intake were examined as exposure factors.UC was considered the outcome.Two-sample Mendelian randomization(TSMR)analysis was performed using methods.Heterogeneity and horizontal pleiotropy assessments were conducted to ensure the robustness of our findings.Additionally,we applied False Discovery Rate(FDR)corrections for multiple tests.Results:The analysis revealed a significant inverse causal relationship between dried fruit intake and UC risk(odds ratio[OR]:0.488,95%confidence interval[CI]:0.261 to 0.915,p=0.025).No significant association was observed between vegetable intake(OR:1.742,95%CI:0.561 to 5.415,p=0.337),processed meat intake(OR:1.136,95%CI:0.552 to 2.339,p=0.729),fresh fruit intake(OR:0.977,95%CI:0.465 to 2.054,p=0.952),cereal intake(OR:1.195,95%CI:0.669 to 2.134,p=0.547).The low heterogeneity observed across analyses and the confirmation of stability through leave-one-out analysis reinforce the reliability of these results.Moreover,after adjusting for multiple tests,none of the dietary factors reached a p-value below the conventional significance threshold of 0.05.Conclusions:This study provides evidence of a potential association between dried fruit intake and a reduced risk of UC.Further MR studies incorporating larger GWAS datasets are needed to confirm these findings.
