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Genetic architecture distinguishes tinnitus from hearing loss

Author

Listed:
  • Royce E. Clifford

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Division of Otolaryngology – Head and Neck Surgery)

  • Adam X. Maihofer

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Department of Psychiatry)

  • Chris Chatzinakos

    (Harvard Medical School, Department of Psychiatry
    Center of Excellence in Depression and Anxiety Disorders)

  • Jonathan R. I. Coleman

    (King’s College London, NIHR Maudsley BRC
    Institute of Psychiatry, Psychology and Neuroscience)

  • Nikolaos P. Daskalakis

    (Harvard Medical School, Department of Psychiatry
    Center of Excellence in Depression and Anxiety Disorders)

  • Marianna Gasperi

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Department of Psychiatry)

  • Kelleigh Hogan

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Department of Psychiatry)

  • Elizabeth A. Mikita

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Department of Psychiatry)

  • Murray B. Stein

    (University of California San Diego, Department of Psychiatry
    Veterans Affairs San Diego Healthcare System, Psychiatry Service
    University of California San Diego, School of Public Health)

  • Catherine Tcheandjieu

    (VA Palo Alto Health Care System)

  • Francesca Telese

    (University of California San Diego, Department of Psychiatry)

  • Yanning Zuo

    (University of California San Diego, Department of Psychiatry)

  • Allen F. Ryan

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Division of Otolaryngology – Head and Neck Surgery)

  • Caroline M. Nievergelt

    (Veterans Affairs San Diego Healthcare System, Research Service
    University of California San Diego, Department of Psychiatry)

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.

Suggested Citation

  • 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 Tchea, 2024. "Genetic architecture distinguishes tinnitus from hearing loss," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44842-x
    DOI: 10.1038/s41467-024-44842-x
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    References listed on IDEAS

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    1. Oleksandr Frei & Dominic Holland & Olav B. Smeland & Alexey A. Shadrin & Chun Chieh Fan & Steffen Maeland & Kevin S. O’Connell & Yunpeng Wang & Srdjan Djurovic & Wesley K. Thompson & Ole A. Andreassen, 2019. "Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Tian Ge & Chia-Yen Chen & Yang Ni & Yen-Chen Anne Feng & Jordan W. Smoller, 2019. "Polygenic prediction via Bayesian regression and continuous shrinkage priors," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Dominic Holland & Oleksandr Frei & Rahul Desikan & Chun-Chieh Fan & Alexey A Shadrin & Olav B Smeland & V S Sundar & Paul Thompson & Ole A Andreassen & Anders M Dale, 2020. "Beyond SNP heritability: Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model," PLOS Genetics, Public Library of Science, vol. 16(5), pages 1-30, May.
    4. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. Caroline M. Nievergelt & Adam X. Maihofer & Torsten Klengel & Elizabeth G. Atkinson & Chia-Yen Chen & Karmel W. Choi & Jonathan R. I. Coleman & Shareefa Dalvie & Laramie E. Duncan & Joel Gelernter & D, 2019. "International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    6. Andrew D. Grotzinger & Mijke Rhemtulla & Ronald Vlaming & Stuart J. Ritchie & Travis T. Mallard & W. David Hill & Hill F. Ip & Riccardo E. Marioni & Andrew M. McIntosh & Ian J. Deary & Philipp D. Koel, 2019. "Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits," Nature Human Behaviour, Nature, vol. 3(5), pages 513-525, May.
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