Zhong Cheng, Wang Li-Hua, Dong Ying, Zhang Haopeng, Ji Lin, Guo Yu
Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, No.274, Zhijiang Middle Road, Jing'an District, Shanghai, China.
School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Indian J Otolaryngol Head Neck Surg. 2025 Aug;77(8):2979-2991. doi: 10.1007/s12070-025-05618-x. Epub 2025 Jun 9.
This study aimed to explore the potential causal relationship between anxiety-depression and tinnitus using a bidirectional mendelian randomization (MR) approach. Utilizing genetic data from five UKB datasets, one IEU dataset, one EBI dataset encompassing traits linked to anxiety and depressive states, and tinnitus data sourced from the FinnGen project, we conducted two-sample MR analyses. Instrumental variables were selected based on stringent criteria, including genome-wide significance, clumping to ensure independence, and the exclusion of palindromic Single Nucleotide Polymorphisms and those associated with confounders. The primary MR analysis employed the Inverse Variance Weighted method, supplemented by sensitivity analyses using the Weighted Median and MR-Egger methods, to address potential pleiotropy. MR analyses suggested a genetic correlation between anxiety-depression and an increased risk of tinnitus. These findings were robust across various sensitivity analyses, including MR-Egger and MR-PRESSO, which supported the absence of pleiotropy and outliers. No evidence of reverse causality was found, strengthening the argument regarding the unidirectional influence of psychological factors on tinnitus. Our results indicate that a genetic predisposition to anxiety and depression can significantly enhance the risk of developing tinnitus. This finding the integration of psychological assessments and interventions in the management of tinnitus, highlighting the importance of addressing mental health components in auditory conditions. Further studies are required to explore these associations in more diverse populations and refine the mechanisms underlying these relationships.
The online version contains supplementary material available at 10.1007/s12070-025-05618-x.
本研究旨在使用双向孟德尔随机化（MR）方法探索焦虑抑郁与耳鸣之间的潜在因果关系。利用来自五个英国生物银行（UKB）数据集、一个国际暴露组学联盟（IEU）数据集、一个包含与焦虑和抑郁状态相关性状的欧洲生物信息学研究所（EBI）数据集以及来自芬兰基因研究项目（FinnGen project）的耳鸣数据，我们进行了两样本MR分析。基于严格标准选择工具变量，包括全基因组显著性、进行聚类以确保独立性，以及排除回文单核苷酸多态性和与混杂因素相关的多态性。主要的MR分析采用逆方差加权法，并辅以使用加权中位数和MR-Egger方法的敏感性分析，以解决潜在的多效性问题。MR分析表明焦虑抑郁与耳鸣风险增加之间存在遗传相关性。这些发现在各种敏感性分析中都很稳健，包括MR-Egger和MR-PRESSO分析，这些分析支持不存在多效性和异常值。未发现反向因果关系的证据，这加强了心理因素对耳鸣单向影响的论点。我们的结果表明，焦虑和抑郁的遗传易感性会显著增加患耳鸣的风险。这一发现为耳鸣管理中整合心理评估和干预提供了依据，凸显了在听觉疾病中解决心理健康因素的重要性。需要进一步研究以在更多样化的人群中探索这些关联，并完善这些关系背后的机制。
在线版本包含可在10.1007/s12070-025-05618-x获取的补充材料。
