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脑功能网络与耳鸣之间的因果关系:一项双向双样本孟德尔随机化研究。

Causal relationships between brain functional networks and tinnitus: A bidirectional 2-sample Mendelian randomization study.

作者信息

Zhong Cheng, Zhang Haopeng, Wang Lihua, Dong Ying, Ji Lin, Guo Yu

机构信息

Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Otolaryngology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Medicine (Baltimore). 2025 Apr 25;104(17):e42328. doi: 10.1097/MD.0000000000042328.

Abstract

This study aimed to discuss the potential causal relationship between brain functional networks and tinnitus using a bidirectional Mendelian randomization (MR) approach. Using genetic data from 6 datasets linked to brain functional networks, and tinnitus data sourced from the FinnGen project, we conducted 2-sample MR analyses. Instrumental variables (IVs) were selected based on stringent criteria, including genome-wide significance, clumping to ensure independence, and exclusion of palindromic single-nucleotide polymorphisms (SNPs) and those associated with confounders. The primary MR analysis employed the inverse variance weighted method supplemented by sensitivity analyses using the weighted median and Mendelian randomization-Egger (MR-Egger) methods to address potential pleiotropy. MR analyses suggested a genetic correlation between functional brain networks and the risk of tinnitus. These findings were robust across various sensitivity analyses, including MR-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier, supporting the absence of pleiotropy and outliers. Our findings provide important evidence for the causal relationship between brain dysfunction and tinnitus, and provide a potential brain function domain reference for the clinical treatment and intervention of tinnitus.

摘要

本研究旨在采用双向孟德尔随机化(MR)方法探讨脑功能网络与耳鸣之间潜在的因果关系。利用来自6个与脑功能网络相关数据集的遗传数据,以及源自芬兰基因项目的耳鸣数据,我们进行了两样本MR分析。基于严格标准选择工具变量(IVs),包括全基因组显著性、聚类以确保独立性,以及排除回文单核苷酸多态性(SNPs)和与混杂因素相关的那些。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孟德尔随机化-埃格(MR-Egger)方法的敏感性分析,以解决潜在的多效性问题。MR分析表明脑功能网络与耳鸣风险之间存在遗传相关性。这些发现在包括MR-Egger和孟德尔随机化多效性残差和异常值在内的各种敏感性分析中都很稳健,支持不存在多效性和异常值。我们的研究结果为脑功能障碍与耳鸣之间的因果关系提供了重要证据,并为耳鸣的临床治疗和干预提供了潜在的脑功能领域参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eca/12039997/2cd524c271a6/medi-104-e42328-g001.jpg

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