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

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.