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| 易怒情绪会导致线粒体功能蛋白异常：来自孟德尔随机化分析的启示 |
| Irritable Mood Leads to Abnormal Mitochondrial Protein Function: Insights from Mendelian Randomization Analysis |
| 投稿时间：2025-07-31 修订日期：2025-07-31 |
| DOI： |
| 中文关键词: 孟德尔随机化，线粒体功能蛋白，精神疾病，易怒情绪，因果关联，发病机制 |
| 英文关键词: Mendelian randomization, mitochondrial function proteins, mental disorders, irritable mood, causal association, pathogenesis |
| 基金项目:贵州省卫健委科学技术基金课题，项目编号：（gzwkj2025-364）；贵州省科技计划贵州省苗医药全省重点实验室建设项目 黔科合平台[2025]018 |
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| 中文摘要: |
| 目的 基于孟德尔随机化分析探讨易怒情绪与线粒体功能蛋白之间的因果关联。 方法 以易怒情绪为暴露，以线粒体功能蛋白为结局，采用逆方差加权法、加权中位数法、MR Egger回归、简单模式、增强模式等模式评估易怒情绪与线粒体功能蛋白表达水平之间的关联。进行反向MR分析。对正向和反向MR分析进行敏感性分析，以确保结果稳定、可靠。
结果 正向MR分析提示，易怒情绪与NFU1存在正向因果关联，（OR：1.88， 95%CI：1.06-3.34，P：0.030），引起NFU1表达升高。反向MR分析提示，丝氨酸蛋白酶HTRA2 （OR: 1.023, 95% CI: 1.004 to 1.044）和琥珀酸脱氢酶组装因子2（OR: 1.016, 95% CI: 1.000 to 1.031）的表达水平与易怒情绪存在显著的正向关联。敏感性分析提示总体结果稳定可靠。结论 本研究通过MR分析发现，易怒情绪会导致NFU1表达升高。反向MR分析提示，两种线粒体功能蛋白丝氨酸蛋白酶HTRA2 和琥珀酸脱氢酶组装因子2 功能异常是遗传预测的易怒情绪型人格的潜在危险因素。这些靶点为理解易怒情绪伤害线粒体功能及通过调节线粒体功能蛋白干预情绪相关疾病提供了思路和参考。 |
| 英文摘要: |
| Abstract：Objective To investigate the causal association between irritable mood and mitochondrial function proteins based on Mendelian randomization (MR) analysis. Methods Irritable mood was set as the exposure, and mitochondrial function proteins were set as the outcomes. The inverse variance weighting method, weighted median method, MR Egger regression, simple mode, and enhanced mode were used to evaluate the association between irritable mood and the expression levels of mitochondrial function proteins. Reverse MR analysis was performed. Sensitivity analyses were conducted for both forward and reverse MR analyses to ensure the stability and reliability of the results. Results Forward MR analysis suggested a positive causal association between irritable mood and NFU1 (OR: 1.88, 95%CI: 1.06–3.34, P: 0.030), indicating that irritable mood increased NFU1 expression. Reverse MR analysis showed significant positive associations between the expression levels of serine protease HTRA2 (OR: 1.023, 95%CI: 1.004–1.044) and succinate dehydrogenase assembly factor 2 (OR: 1.016, 95%CI: 1.000–1.031) and irritable mood. Sensitivity analyses confirmed the overall stability and reliability of the results. Conclusion This MR analysis revealed that irritable mood leads to increased NFU1 expression. Reverse MR analysis indicated that abnormal functions of two mitochondrial function proteins, serine protease HTRA2 and succinate dehydrogenase assembly factor 2, are potential risk factors for genetically predicted irritable mood personality. These targets provide insights and reference for understanding how irritable mood impairs mitochondrial function and for intervening in mood-related diseases by regulating mitochondrial function proteins. |
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