Nature Communications (Jan 2024)

Genetic architecture distinguishes tinnitus from hearing loss

  • Royce E. Clifford,
  • Adam X. Maihofer,
  • Chris Chatzinakos,
  • Jonathan R. I. Coleman,
  • Nikolaos P. Daskalakis,
  • Marianna Gasperi,
  • Kelleigh Hogan,
  • Elizabeth A. Mikita,
  • Murray B. Stein,
  • Catherine Tcheandjieu,
  • Francesca Telese,
  • Yanning Zuo,
  • Allen F. Ryan,
  • Caroline M. Nievergelt

DOI
https://doi.org/10.1038/s41467-024-44842-x
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 16

Abstract

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Abstract Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.