Zhao Ying, Yu Cong, Sun Hengchang, Xie Fangmei, Shen Jian, Li Xiaoming, Song Xiaoyu, Luo Wenfeng, He Jinhua, Han Zeping
Central Laboratory, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
Clinical Laboratory Department, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
PLoS One. 2025 May 19;20(5):e0322898. doi: 10.1371/journal.pone.0322898. eCollection 2025.
Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined by the rapid onset of hearing impairment without an identifiable etiology. The decreased serum concentrations of 25-hydroxyvitamin D(25(OH)D) was shown to be associated with decreased hearing ability. However, current cross-sectional studies have only demonstrated an association, failing to establish a causal link. Therefore, a comprehensive investigation is necessary to clarify the causal relationship between them. Analysis was done by using largescale genome-wide association analysis(GWAS) summary datasets to give information about the incidence of ISSNHL and genetically predicted serum 25(OH)D levels by a two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) were identified as genome-wide significant single-nucleotide polymorphisms (SNPs) with a significance threshold of P < 1 × 10-8 and an independence criterion of r2 < 0.001. The GWAS data on serum 25-hydroxyvitamin D levels comprised 6,896,093 SNPs from 496,949 individuals of European ancestry (exposure variable). Outcome data were derived from another GWAS data, including 16,380,424 SNPs from 1,491 European ISSNHL cases and 196,592 controls. MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and weighted mode, were used to assess causal effects. Heterogeneity tests, horizontal pleiotropy tests, and the leave-one-out method were applied to evaluated the robustness of the MR analysis results. A total of 117 SNPs were employed as instrumental variables (P < 5 × 10-8). Our results indicated no causal association between serum 25(OH) D levels and the risk of ISSNHL within the European population (IVW; OR = 1.09, 95% CI = 0.81 to 1.48, P = 0.573). Furthermore, the statistical models did not reveal any evidence of heterogeneity or pleiotropy.
特发性突发性感音神经性听力损失（ISSNHL）的定义是听力障碍迅速发作且无明确病因。血清25-羟基维生素D（25(OH)D）浓度降低与听力下降有关。然而，目前的横断面研究仅证明了一种关联，未能建立因果关系。因此，有必要进行全面调查以阐明它们之间的因果关系。通过使用大规模全基因组关联分析（GWAS）汇总数据集进行分析，通过两样本孟德尔随机化（MR）分析提供有关ISSNHL发病率和基因预测的血清25(OH)D水平的信息。将工具变量（IVs）鉴定为全基因组显著的单核苷酸多态性（SNPs），其显著性阈值为P < 1×10-8，独立标准为r2 < 0.001。血清25-羟基维生素D水平的GWAS数据包括来自496,949名欧洲血统个体的6,896,093个SNPs（暴露变量）。结果数据来自另一个GWAS数据，包括来自1,491例欧洲ISSNHL病例和196,592例对照的16,380,424个SNPs。采用MR-Egger、逆方差加权（IVW）、加权中位数、简单模式和加权模式来评估因果效应。应用异质性检验、水平多效性检验和留一法来评估MR分析结果的稳健性。总共117个SNPs被用作工具变量（P < 5×10-8）。我们的结果表明，在欧洲人群中，血清25(OH)D水平与ISSNHL风险之间无因果关联（IVW；OR = 1.09，95%CI = 0.81至1.48，P = 0.573）。此外，统计模型未显示任何异质性或多效性的证据。
