Ahmed Samah, Vaden Kenneth I, Leitao Darren, Dubno Judy R, Drögemöller Britt I
Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Hearing Research Program, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, South Carolina, Charleston, USA.
medRxiv. 2025 Jan 15:2025.01.14.24318673. doi: 10.1101/2025.01.14.24318673.
Age-related hearing loss affects one-third of the population over 65 years. However, the diverse pathologies underlying these heterogenous phenotypes complicate genetic studies. To overcome challenges associated with accurate phenotyping for older adults with hearing loss, we applied computational phenotyping approaches based on audiometrically measured hearing loss. This novel phenotyping strategy uncovered distinct genetic variants associated with sensory and metabolic hearing loss. Sex-stratified analyses of these sexually dimorphic hearing loss phenotypes revealed a novel locus of relevance to sensory hearing loss in males, but not females. Enrichment analyses revealed that genes involved in frontotemporal dementia were implicated in metabolic hearing loss, while genes relating to sensory processing of sound by hair cells were implicated in sensory hearing loss. Our study has enhanced our understanding of these two distinct hearing loss phenotypes, representing the first step in the development of more precise treatments for these pathologically distinct hearing loss phenotypes.
年龄相关性听力损失影响着三分之一的65岁以上人群。然而，这些异质表型背后的多种病理情况使基因研究变得复杂。为了克服与听力损失老年成人准确表型分析相关的挑战，我们应用了基于听力测量的听力损失的计算表型分析方法。这种新颖的表型分析策略发现了与感觉性和代谢性听力损失相关的不同基因变异。对这些性别二态性听力损失表型的性别分层分析揭示了一个与男性感觉性听力损失相关的新位点，而女性则没有。富集分析表明，与额颞叶痴呆相关的基因与代谢性听力损失有关，而与毛细胞声音感觉处理相关的基因与感觉性听力损失有关。我们的研究增进了我们对这两种不同听力损失表型的理解，代表了为这些病理上不同的听力损失表型开发更精确治疗方法的第一步。
