Work

The Genetic and Transcriptomic Nexus of Age-Related Hearing Loss and Alzheimer’s Disease

Year: 2026

Type: article

Abstract: Introduction: Despite the recognized association between age-related hearing loss (ARHL) and Alzheimer’s disease (AD), the genetic relationship and shared transcriptional mechanisms between them remain largely unexplored. Methods: We systematically investigated the ARHL-AD axis using a multi-layered genomic strategy, incorporating causal inference, cis-eQTL mediation, Bayesian colocalization, and independent replication cohort validation. Results: Genetically predicted ARHL was associated with a reduced risk of overall AD and its early/late-onset subtypes, with no evidence of reverse causality in reverse MR analyses. Among 36 identified mediating genes, CSK showed the most consistent mediation signals across discovery and replication cohorts, although the replication was statistically partial (Sobel p = 0.078). Pathway analyses revealed that these genetic links predominantly involve Wnt signaling and endoplasmic reticulum protein processing. Discussion: Our integrative multi-omics findings suggest a potential genetic association between ARHL liability and AD risk. More importantly, we identified a prioritized CSK-driven transcriptional network, providing novel mechanistic insights and highlighting a candidate gene for future functional investigation in neurodegeneration.

Source: Genes

DOI: 10.3390/genes17070776

Authors: Kaige Deng, Xu Deng, Siying Li, Shubin Fang, Fanqin Wei

Institutions: Sun Yat-sen University, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Medical College, South China University of Technology

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137