Abstract: Objective To investigate the causal relationship between rheumatoid arthritis(RA), intrinsic emotions, and coronary atherosclerosis(CAs), providing a basis for improving the comprehensive management of cardiovascular risk in RA patients. Methods A two-sample Mendelian randomization(MR)approach was employed, with instrumental variables(IVs)selected from public genome-wide association study(GWAS)databases. The primary analysis method was inverse-variance weighted(IVW), with a random-effects model used in the presence of heterogeneity. MR-Egger regression, leave-one-out analysis, and reverse MR were conducted to assess the robustness of the results. Multivariable MR and mediation analysis were performed to evaluate the mediating role of intrinsic emotions. Results A positive causal association was found between RA and CAs(OR=1.035, 95%CI: 1.011-1.060, P<0.05). Additionally, a causal relationship was observed between RA and intrinsic emotions(pain: OR=1.006, 95%CI: 1.001-1.010, P<0.05; nervousness: OR=1.006, 95%CI: 1.000-1.011, P<0.05; depression: OR=1.006, 95%CI: 1.001-1.011, P<0.05). There was also a causal association between intrinsic emotions and CAs(pain: OR=1.840, 95%CI: 1.295-2.614,P<0.05; nervousness: OR=1.388, 95%CI: 1.141-1.689,P<0.05; depression: OR=1.561, 95%CI: 1.195-2.039, P<0.05). Mediation analysis revealed that intrinsic emotions partially mediated the causal pathway between RA and CAs, with effect proportions of 11.76%, 5.88%, and 8.82%, respectively. MR-Egger regression did not detect horizontal pleiotropy, and reverse MR analysis suggested no reverse causality. Conclusion Both RA and intrinsic emotions have positive causal associations with CAs, with intrinsic emotions playing a partial mediating role in this relationship.

Key words: Rheumatoid arthritis, Internal emotion, Coronary atherosclerosis, Genetic prediction, Mendelian randomization