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Conventional and Shared Genetic Association Analysis Between Diabetes Mellitus and Sensorineural Hearing Loss.

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Title: Conventional and Shared Genetic Association Analysis Between Diabetes Mellitus and Sensorineural Hearing Loss.
Authors: Wang X; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Zhang Z; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Qiu K; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Luo Y; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK, bristol.ac.uk., Yi X; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Pang W; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Jiang D; Department of Pathology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Ren J; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn., Zhao Y; Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, China, scu.edu.cn.
Source: Human mutation [Hum Mutat] 2026 Sep 15; Vol. 2026, pp. 5099141. Date of Electronic Publication: 2026 Sep 15 (Print Publication: 2026).
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9215429 Publication Model: eCollection Cited Medium: Internet ISSN: 1098-1004 (Electronic) Linking ISSN: 10597794 NLM ISO Abbreviation: Hum Mutat Subsets: MEDLINE
Imprint Name(s): Original Publication: New York : Wiley-Liss, c1992-
MeSH Terms: Hearing Loss, Sensorineural*/genetics , Hearing Loss, Sensorineural*/epidemiology , Diabetes Mellitus, Type 2*/genetics , Diabetes Mellitus, Type 2*/epidemiology , Diabetes Mellitus, Type 2*/complications , Genetic Predisposition to Disease* , Genetic Association Studies*, Humans ; Female ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Linkage Disequilibrium ; Aged
Abstract: Purpose: This study aims to investigate the epidemiological and genetic associations between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) across different subtypes.
Methods: We analyzed 502,490 participants from the UK Biobank using multivariate logistic regression to examine the association between DM and SNHL, considering gender, age, and HbA1c levels. Genetic correlations and causality were examined by linkage disequilibrium score regression and bidirectional Mendelian randomization. Cross-trait meta-analyses identified shared loci between DM and SNHL, followed by gene annotation, functional analysis, and drug candidate exploration for the shared traits.
Results: Observational analysis revealed significant associations between DM and SNHL, consistent in subgroups based on age, sex, and certain HbA1c levels. A positive genetic correlation was found between type 2 diabetes mellitus (T2D) and SNHL (Rg = 0.0982, p = 0.0095) between T2D and SNHL, and four loci were identified, with ARHGEF28 and TCF7L2 prioritized as credible pleiotropic genes. Enrichment was indicated in glucose metabolism and organogenesis, with shared heritability in metabolic tissues and outer hair cells. Metformin was identified as potential drug candidates for the T2D-SNHL comorbidity.
Conclusion: These findings progress our understanding of the epidemiological association, shared genetic basis, and potential therapeutic targets between T2D and SNHL, which might contribute to the management of their comorbidity.
(Copyright © 2026 Xiaoyu Wang et al. Human Mutation published by John Wiley & Sons Ltd.)
Competing Interests: The authors declare no conflicts of interest.
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Contributed Indexing: Keywords: cross-sectional analysis; diabetes; genetic correlation; sensorineural hearing loss
Entry Date(s): Date Created: 20260916 Date Completed: 20260916 Latest Revision: 20260917
Update Code: 20260917
PubMed Central ID: PMC13576905
DOI: 10.1155/humu/5099141
PMID: 42746577
Database: MEDLINE
Description
ISSN:1098-1004
DOI:10.1155/humu/5099141