Based on the resting-state functional magnetic resonance imaging reveals the causal relationship between the brain function network and the risk of tinnitus: a bidirectional Mendelian randomization analysis

Objectives Tinnitus affects millions worldwide. Its neural mechanisms remain unclear. This study aimed to explore the causal relationships between brain functional networks and tinnitus risk using Mendelian randomization (MR) analyses. Methods We performed MR analyses using brain activity data from resting-state functional magnetic resonance imaging (rsfMRI) and genetic data from genome-wide association studies (GWAS). A total of 191 brain features, including amplitude traits and functional connectivity measures, were selected based on their genetic associations. Results Forward MR analyses showed that increased activity in the parietal and inferior frontal regions was associated with a 41% reduction in tinnitus risk (OR = 0.59, p  = 1.8 × 10 ^–4 ). In contrast, increased activity in the precuneus, angular gyrus, and frontal areas was linked to a 49% increase in tinnitus risk (OR = 1.49, p  = 8.9 × 10 ^–4 ). Activities in the parietal and inferior frontal regions were negatively correlated with tinnitus risk (OR = 0.72, p  = 0.0037). Additionally, higher activity in the parietal, frontal, and temporal regions doubled the risk (OR = 2.02, p  = 0.015). Reverse MR showed that stronger connectivity between frontal and temporal regions was inversely related to tinnitus risk (OR = 0.95, p  = 0.049). Conclusions Specific brain activity and connectivity patterns are causally linked to tinnitus.