Genomic and Epigenomic Advances in Hearing Loss: Molecular Mechanisms, Diagnostics, and Emerging Therapies

<b>Background:</b> Hearing loss is a widespread sensory disorder affecting over 1.5 billion people worldwide, with the number projected to exceed 700 million by 2050. It imposes social and economic burdens across all ages and regions. Approximately half of adult cases are preventable, but the underlying causes are complex, with 75-80% due to autosomal recessive genetic factors and key roles for mutations in genes such as GJB2. Advances in sequencing technologies have accelerated gene discovery, but challenges remain in interpreting variants. Epigenetic mechanisms such as DNA methylation and histone modifications are increasingly recognized as crucial in auditory biology and could offer new biomarkers and therapeutic targets. Integrating epidemiological, genetic, and epigenomic data is essential to developing targeted prevention and treatment strategies to reduce the global burden of hearing loss. <b>Methods:</b> This narrative review examines recent genomic and epigenomic advances in hearing loss, with particular emphasis on molecular mechanisms, emerging diagnostic applications, and translational therapeutic opportunities. A comprehensive review of current epidemiological data, genetic studies, and epigenomic research was conducted using the peer-reviewed literature from international databases. Key areas of interest include inheritance patterns, molecular pathways, and recent advances in omics technologies. <b>Results:</b> Epigenetic mechanisms, including DNA methylation and histone modifications, are increasingly recognized as important regulators of cochlear development and hair cell survival, although much of the current evidence remains preclinical. Studies suggest that peripheral epigenetic signatures may serve as biomarkers for early diagnosis and risk stratification. <b>Conclusions:</b> Integrating established screening pathways with epidemiological trends and molecular knowledge offers a promising path toward precision medicine in hearing care. Connecting these domains is essential to developing equitable and effective interventions and addressing persistent global disparities in hearing health. This review highlights the evolving landscape of auditory genetics and epigenetics and outlines future directions for translational research and personalized therapy.