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

IF 1.8 2区医学 Q2 GENETICS & HEREDITY

Human Mutation Pub Date : 2026-09-15 DOI:10.1155/humu/5099141

Xiaoyu Wang, Ziyan Zhang, Ke Qiu, Yaxin Luo, Xiaowei Yi, Wendu Pang, Dan Jiang, Jianjun Ren, Yu Zhao

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引用次数: 0

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.

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糖尿病与感音神经性听力损失的常规和共享遗传关联分析。

目的：探讨不同亚型糖尿病（DM）与感音神经性听力损失（SNHL）的流行病学和遗传关系。方法：考虑性别、年龄和HbA1c水平，我们分析了来自UK Biobank的502490名参与者，使用多变量logistic回归来研究DM和SNHL之间的关系。通过连锁不平衡评分回归和双向孟德尔随机化检验遗传相关性和因果关系。跨性状荟萃分析确定了DM和SNHL之间的共享位点，随后进行了基因注释、功能分析和候选药物探索。结果：观察性分析显示DM和SNHL之间存在显著关联，在基于年龄、性别和特定HbA1c水平的亚组中是一致的。2型糖尿病（T2D）与SNHL之间存在正相关遗传关系（Rg = 0.0982, p = 0.0095），并鉴定出4个基因座，其中ARHGEF28和TCF7L2优先作为可靠的多效基因。富集在葡萄糖代谢和器官发生中，在代谢组织和外毛细胞中具有共同的遗传力。二甲双胍被确定为T2D-SNHL合并症的潜在候选药物。结论：这些发现促进了我们对T2D和SNHL之间的流行病学关联、共同的遗传基础和潜在的治疗靶点的理解，可能有助于其合并症的管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.