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<p>Disequilibrium is a highly prevalent age-related condition that increases fall risk, yet the genetic architecture underlying vestibular function remains poorly defined. Here, we performed genome-wide association studies (GWAS) of vestibular-evoked potentials (VsEP) and raised-beam performance across young and aged Hybrid Mouse Diversity Panel (HMDP) strains. In young mice, we identified genome-wide significant loci on chromosomes 4, 7, 14, and 15, along with suggestive associations on chromosomes 6 and 14. To refine candidate genes, we integrated cochlear and cerebellar cis-eQTL data from BXD strains with human cochlear transcriptomic profiles, revealing 12 cochlea-enriched genes within linkage disequilibrium intervals. Single-cell RNA sequencing localized <i>Agbl4</i>, <i>Cntnap2</i>, <i>Dmc1</i>, and <i>Pcdh20</i> to vestibular hair cells, and <i>Gpnmb</i> to melanocytes of the inner ear. These findings highlight coordinated contributions of sensory and non-sensory cell types to vestibular performance. Although no significant loci were detected in aged mice, our integrative genetic and transcriptomic framework provides new insight into the molecular architecture of vestibular function and potential pathways underlying age-related balance impairment.</p>

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Novel candidate genes for vestibular function identified through GWAS in the hybrid mouse diversity panel

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Yuzuru Ninoyu,
  • Calvin Pan,
  • Jennifer Luu,
  • Sameeha Rashid,
  • Jadyn Johnston,
  • Briana Ortega,
  • Ely Boussaty,
  • Lu Lu,
  • Royce Clifford,
  • Pejman Mohammadi,
  • Francesca Telese,
  • Abraham A. Palmer,
  • Aldons J. Lusis,
  • Rick A. Friedman

摘要

Disequilibrium is a highly prevalent age-related condition that increases fall risk, yet the genetic architecture underlying vestibular function remains poorly defined. Here, we performed genome-wide association studies (GWAS) of vestibular-evoked potentials (VsEP) and raised-beam performance across young and aged Hybrid Mouse Diversity Panel (HMDP) strains. In young mice, we identified genome-wide significant loci on chromosomes 4, 7, 14, and 15, along with suggestive associations on chromosomes 6 and 14. To refine candidate genes, we integrated cochlear and cerebellar cis-eQTL data from BXD strains with human cochlear transcriptomic profiles, revealing 12 cochlea-enriched genes within linkage disequilibrium intervals. Single-cell RNA sequencing localized Agbl4, Cntnap2, Dmc1, and Pcdh20 to vestibular hair cells, and Gpnmb to melanocytes of the inner ear. These findings highlight coordinated contributions of sensory and non-sensory cell types to vestibular performance. Although no significant loci were detected in aged mice, our integrative genetic and transcriptomic framework provides new insight into the molecular architecture of vestibular function and potential pathways underlying age-related balance impairment.