| Title: | Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis |
| Journal: | European Journal of Human Genetics |
| Published: | 7 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40055553/ |
| DOI: | https://doi.org/10.1038/s41431-025-01789-x |
Publication 14645
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Abstract
Age-related (AR) hearing loss (HL) is the most prevalent sensorineural disorder in older adults. Here we demonstrate that rare-variants in well-established Mendelian HL genes play an important role in ARHL etiology. In all we identified 32 Mendelian HL genes which are associated with ARHL. We performed single and rare-variant aggregate association analyses using exome data obtained from white-Europeans with self-reported hearing phenotypes from the UK Biobank. Our analysis revealed previously unreported associations between ARHL and rare-variants in Mendelian non-syndromic and syndromic HL genes, including MYO15A, and WFS1. Additionally, rare-variant aggregate association analyses identified associations with Mendelian HL genes i.e., ACTG1, GRHL2, KCNQ4, MYO7A, PLS1, TMPRSS3, and TNRC6B. Four novel ARHL genes were also detected: FBXO2 and PALM3, implicated in HL in mice, TWF1, associated with HL in Dalmatian dogs, and TXNDC17. In-silico analyses provided further evidence of inner ear expression of these genes in both murine and human models, supporting their relevance to ARHL. Analysis of variants with minor allele frequency >0.005 revealed additional ARHL associations with known e.g., ILDR1 and novel i.e., ABHD12, COA8, KANSL1, SERAC1, and UBE3B Mendelian non-syndromic and syndromic HL genes as well as ARHL associations with genes that have not been previously reported to be involved in HL e.g., VCL. Rare-variants in Mendelian HL genes typically exhibited higher effect sizes for ARHL compared to those in other associated genes. In conclusion, this study highlights the critical role Mendelian non-syndromic and syndromic HL genes play in the etiology of ARHL.</p>
7 Authors
- Diana M. Cornejo-Sanchez
- Thashi Bharadwaj
- Rui Dong
- Gao T. Wang
- Isabelle Schrauwen
- Andrew T. DeWan
- Suzanne M. Leal
1 Application
| Application ID | Title |
|---|---|
| 32285 | Detecting pleiotropic effects through integration of omics data |
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