Causal Effects Between Anxiety-Depressive and Subjective Tinnitus in Europe: A Bidirectional Mendelian Randomization Study

TL;DR

This study finds that a genetic predisposition to anxiety and depression increases the risk of developing tinnitus, suggesting the importance of mental health in managing auditory conditions.

Contribution

The study provides novel evidence of a unidirectional causal effect from anxiety-depression to tinnitus using bidirectional Mendelian randomization.

Findings

A genetic predisposition to anxiety and depression increases the risk of tinnitus.

No evidence of reverse causality was found, indicating psychological factors influence tinnitus.

Findings were robust across multiple sensitivity analyses, supporting a unidirectional relationship.

Abstract

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.

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