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

Cheng Zhong1, Haopeng Zhang2, Lihua Wang2

  • 1Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

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This study explored the link between brain function and tinnitus using genetic data. Findings suggest brain functional networks may causally influence tinnitus risk, offering insights for treatment.

Keywords:
Mendelian randomizationbrain functional networkscausalitytinnitus

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Area of Science:

  • Neuroscience
  • Genetics
  • Epidemiology

Background:

  • Tinnitus is a common auditory disorder with complex etiology.
  • The relationship between brain functional networks and tinnitus risk remains unclear.
  • Understanding genetic predispositions can elucidate causal pathways.

Purpose of the Study:

  • To investigate the potential causal relationship between brain functional networks and tinnitus.
  • To utilize a bidirectional Mendelian randomization approach for robust genetic analysis.
  • To identify potential therapeutic targets within brain function domains.

Main Methods:

  • Employed a 2-sample Mendelian randomization (MR) design.
  • Utilized genetic data from 6 brain functional network datasets and the FinnGen project for tinnitus.
  • Selected instrumental variables based on stringent criteria (genome-wide significance, independence, confounder exclusion).
  • Applied inverse variance weighted (IVW) method, supplemented by weighted median and MR-Egger sensitivity analyses.

Main Results:

  • MR analyses indicated a significant genetic correlation between functional brain networks and tinnitus risk.
  • Sensitivity analyses (MR-Egger, MR-PRESSO) confirmed the robustness of findings and absence of significant pleiotropy.
  • Results support a potential causal link from brain functional networks to tinnitus development.

Conclusions:

  • This study provides genetic evidence supporting a causal relationship between brain dysfunction and tinnitus.
  • Findings highlight the role of brain functional networks in tinnitus etiology.
  • Results offer a potential neurobiological basis for clinical interventions and treatment strategies for tinnitus.