Large-scale audiometric phenotyping identifies distinct genes and pathways involved in hearing loss subtypes
Age-related hearing loss affects one-third of the population over 65 years. However, the diverse pathologies underlying these heterogeneous phenotypes complicate genetic studies. Here we show that by applying computational phenotyping approaches based on audiometrically measured hearing loss, we can overcome challenges associated with accurate phenotyping for older adults with hearing loss. Using this phenotyping strategy, we uncover differences in the associations observed between genetic variants and sensory and metabolic hearing loss. Sex-stratified analyses of these sexually dimorphic hearing loss phenotypes reveal a locus of relevance to sensory hearing loss in males, but not females. Enrichment analyses implicate genes involved in frontotemporal dementia in metabolic hearing loss, while genes relating to sensory processing of sound by hair cells are implicated in sensory hearing loss. Our study enhances our understanding of these two hearing loss phenotypes, representing the first step in the development of more precise treatments for these pathologically distinct hearing loss phenotypes.
Authors
- Britt I. Drögemöller (ORCID: https://orcid.org/0000-0002-3348-5855)
- Kenneth I. Vaden (ORCID: https://orcid.org/0000-0002-3621-2043)
- Morag A. Lewis (ORCID: https://orcid.org/0000-0002-1846-8600)
- Karen P. Steel (ORCID: https://orcid.org/0000-0002-8019-5359)
- Judy R. Dubno (ORCID: https://orcid.org/0000-0003-2340-4721)
- Samah Ahmed
- D. Leitão
Institutions
- Medical University of South Carolina (US)
- King's College London (GB)
- Research Manitoba (CA)
- CancerCare Manitoba (CA)
- Children's Hospital Research Institute of Manitoba (CA)
- Children's Hospital of Winnipeg (CA)
- Research Institute in Oncology and Hematology (CA)
- University of Manitoba (CA)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1038/s42003-025-08778-2
- Citations
- 3
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 4.39
Funders
- Research Manitoba
- University of South Carolina
- Government of Canada
- National Institutes of Health
- South Carolina Clinical and Translational Research Institute, Medical University of South Carolina
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute on Deafness and Other Communication Disorders
- National Center for Research Resources
- National Center for Advancing Translational Sciences