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| 抑郁症与耳鸣的关系：两样本与多变量孟德尔随机化分析[ 作者简介：柴泽锟（1999-），男，北京中医药大学第二临床医学院，2022级硕士研究生，研究方向：中医内科学脑病方向，E-mail:bucmczk@163.com。 通讯作者：王乐（1978-），男，主任医师，硕士研究生导师，北京中医药大学第二临床医学院副院长，研究方向：中医内科学脑病方向,E-mail:13661172704@139.com。 基金项目：国家自然科学基金，项目批准号：82374275。 ] |
| The relationship between depression and tinnitus: Two-sample and multivariable Mendelian randomization analysis |
| 投稿时间：2025-08-01 修订日期：2025-08-01 |
| DOI： |
| 中文关键词: 关键词：抑郁症 失眠 耳鸣 两样本孟德尔随机化 多变量孟德尔随机化。 |
| 英文关键词: Keywords: depression Insomnia Tinnitus Mendelian randomization of two samples Multivariate Mendelian randomization. |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| 中文摘要: |
| 摘要： 目的：采用两样本孟德尔随机化（TwoSampleMR）以及多变量孟德尔随机化(multivariable Mendelian randomization, MVMR)的研究方法，探讨抑郁症与耳鸣之间的因果关系。方法：利用IEU OpenGWASproject网站获取抑郁症及耳鸣的全基因组关联研究（GWAS）数据，使用两样本与多变量孟德尔随机化分析的方法探讨抑郁症与耳鸣的因果关系；孟德尔随机化分析中使用逆方差加权法（inverse variance weighted，IVW）、加权中位数（Weighted median，WME）和MR-Egger法进行孟德尔随机化分析。同时采用Egger intercept检测水平多效性，留一法（Leave-one-out）进行敏感性分析，保证结果稳健性。最后使用多变量孟德尔随机化分析法，探讨耳鸣的另一危险因素失眠是否参与抑郁症对耳鸣的影响，观察三者之间的因果关系。结果：抑郁症与耳鸣发生之间呈正相关（IVW：OR=1.0304,95%CI:1.0163~1.0447，P=2.0214*10-5）；在矫正了失眠与抑郁症彼此间的影响后，抑郁症与耳鸣发生之间呈正相关（MVMR：OR=1.0280,95%CI:1.0108~1.0456，P=0.0014）；失眠与耳鸣发生之间呈正相关（IVW：OR=1.0312,95%CI:0.9818~1.0830，P=0.2205），但没有统计学意义。所有分析的Egger intercept的值和0没有显著统计学差异（P＞0.05）,表明没有水平多效性；Leave-one-out法显示结果稳定，未检测到对结果影响大的单核苷酸多态性（SNPs）；全部F值大于10，提示不存在弱工具变量（IVs）偏倚。结论：抑郁症与耳鸣的发生呈正相关，稳定性分析显示结果可靠。在矫正了失眠与抑郁症彼此间的影响后，抑郁症依然与耳鸣的发生生呈正相关，但失眠与耳鸣的关系无统计学意义，提示抑郁症会导致耳鸣的产生，其影响与失眠无关；失眠导致耳鸣的原因，可能是以抑郁症为中介产生的因果效应。 |
| 英文摘要: |
| Abstract: Objective: To explore the causal relationship between depression and tinnitus by using two-sample Mendelian randomization (TwoSampleMR) and multivariable Mendelian randomization (MVMR).Methods:The genome-wide association study (GWAS) data of depression and tinnitus were obtained from the IEU OpenGWASproject website, and the causal relationship between depression and tinnitus was explored by two-sample and multivariate Mendelian randomization analysis. Mendelian randomization analysis was performed using inverse variance weighted (IVW), weighted median (WME) and MR-Egger method in Mendelian randomization analysis. At the same time, the Egger intercept detection level pleiotropy and the leave-one-out method were used for sensitivity analysis to ensure the robustness of the results. Finally, multivariate Mendelian randomization analysis was used to explore whether insomnia, another risk factor for tinnitus, was involved in the influence of depression on tinnitus, and the causal relationship between the three was observed.Results: There was a positive correlation between depression and tinnitus (IVW: OR=1.0304, 95%CI: 1.0163~1.0447, P=2.0214*10-5). After correcting for the effects of insomnia and depression, there was a positive correlation between depression and tinnitus (MVMR:OR=1.0280, 95%CI:1.0108~1.0456, P=0.0014). There was a positive correlation between insomnia and tinnitus (IVW: OR=1.0312, 95%CI: 0.9818~1.0830, P=0.2205), but there was no statistical significance. There was no statistically significant difference in the value and 0 of the Egger intercept analyzed (P>0.05), indicating no horizontal pleiotropy; The Leave-one-out method showed stable results, and no single nucleotide polymorphisms (SNPs) that had a significant impact on the results were detected. All F-scores greater than 10 indicate no weakly instrumental variable (IVs) bias.Conclusion: There is a positive correlation between depression and tinnitus, and stability analysis shows that the results are reliable. After correcting for the effects of insomnia and depression, depression was still positively correlated with the occurrence of tinnitus, but the relationship between insomnia and tinnitus was not statistically significant, suggesting that depression would lead to tinnitus, and its effect was not related to insomnia. The cause of insomnia causing tinnitus may be a causal effect mediated by depression. |
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