内在情感与类风湿关节炎患者冠状动脉粥样硬化风险关系的孟德尔随机化分析

doi:10.6040/j.issn.1671-7554.0.2025.0604

摘要/Abstract

摘要： 目的探讨类风湿关节炎(rheumatoid arthritis, RA)、内在情感与冠状动脉粥样硬化(coronary atherosclerosis, CAs)之间的因果关系,为完善RA患者心血管风险的综合管理提供依据。方法采用两样本孟德尔随机化(mendelian randomization, MR)方法,从公开全基因组关联研究(genome-wide association study, GWAS)数据库筛选工具变量(instrumental variables, IVs)。以逆方差加权法(inverse-variance weighted, IVW)主要分析方法,存在异质性时采用随机效应模型,并通过MR-Egger回归、留一法及反向MR分析验证结果稳健性;运用多变量MR与中介效应分析评估内在情感的中介作用。结果 RA与CAs存在正向因果关联(OR=1.035,95%CI:1.011~1.060,P<0.05),且RA与内在情感存在因果关联(感到痛苦OR=1.006,95%CI:1.001~1.010,P<0.05;神经过敏OR=1.006,95%CI:1.000~1.011,P<0.05;抑郁情绪OR=1.006,95%CI:1.001~1.011,P<0.05)。内在情感与CAs之间存在因果关联(感到痛苦:OR=1.840,95%CI: 1.295~2.614,P<0.05;神经过敏:OR=1.388,95%CI: 1.141~1.689,P<0.05;抑郁情绪:OR=1.561,95%CI: 1.195~2.039,P< 0.05)。中介效应分析显示,内在情感在RA与CAs的因果路径中发挥部分中介作用,效应比例分别为11.76%、5.88%与8.82%。MR-Egger回归未发现水平多效性,反向MR分析提示不存在反向因果。结论 RA与内在情感均与CAs存在正向因果关联,且内在情感在其中发挥部分中介作用。

关键词: 类风湿关节炎, 内在情感, 冠状动脉粥样硬化, 基因预测, 孟德尔随机化

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

中图分类号:

R684.3

段盈竹,董波,于睿. 内在情感与类风湿关节炎患者冠状动脉粥样硬化风险关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2026, 64(4): 63-71.

DUAN Yingzhu, DONG Bo, YU Rui. Mendelian randomization study on the association of intrinsic emotions with coronary atherosclerosis risk in patients with rheumatoid arthritis[J]. Journal of Shandong University (Health Sciences), 2026, 64(4): 63-71.

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