{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:14:07Z","timestamp":1783660447716,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515012713"],"award-info":[{"award-number":["2023A1515012713"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Despite the recognized association between age-related hearing loss (ARHL) and Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/genes17070776","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Genetic and Transcriptomic Nexus of Age-Related Hearing Loss and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4816-348X","authenticated-orcid":false,"given":"Kaige","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangdong Medical University, Dongguan 523808, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, South China University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanqin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0140-6736(21)00516-X","article-title":"Hearing loss prevalence and years lived with disability, 1990\u20132019: Findings from the Global Burden of Disease Study 2019","volume":"397","author":"Haile","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/archneurol.2010.362","article-title":"Hearing loss and incident dementia","volume":"68","author":"Lin","year":"2011","journal-title":"Arch. 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