BackgroundA growing body of evidence suggests that immunological processes have a significant role in developing idiopathic sudden sensorineural hearing loss (SSHL). However, few studies have examined the association between immune cell phenotype and SSHL using Mendelian Randomization (MR).MethodsThe online genome-wide association studies (GWAS) database was used to compile data from GWAS covering 731 immunophenotypes and SSHL. Inverse variance weighted (IVW) analysis was primarily used for MR study, and single nucleotide polymorphisms (SNPs) associated with immunophenotypes served as dependent variables. A sensitivity study and the false discovery rate (FDR) correction were used to examine the MR hypothesis. In addition, the possibility of reverse causality between immunophenotype and SSHL was validated by reverse MR. Reverse MR was analyzed in a manner consistent with forward MR.ResultsAfter FDR correction and sensitivity analysis, we screened 7 immunophenotypes, including IgD+ CD38dim %lymphocyte (95% CI: 1.0019, 1.0742, p = 3.87 × 10−2, FDR = 1.15 × 10−2); Unsw mem AC (95% CI: 1.004, 1.2522, p = 4.23 × 10−2, FDR = 2.25 × 10−2); CD86+ myeloid DC AC (95% CI: 1.0083, 1.1147, p = 2.24 × 10−2, FDR = 4.27 × 10−2); CD33dim HLA DR− AC (95% CI: 1.0046, 1.0583, p = 2.12 × 10−2, FDR = 4.69 × 10−2); SSC-A on CD8br (95% CI: 1.0028, 1.1461, p = 4.12 × 10−2, FDR = 4.71 × 10−2); CD45RA− CD4+ %T cell (95% CI: 1.0036, 1.0503, p = 2.32 × 10−2, FDR = 4.82 × 10−2); DP (CD4+CD8+) AC (95% CI: 1.011, 1.2091, p = 2.78 × 10−2, FDR = 4.97 × 10−2). There was a strong causal relationship with SSHL onset, and the reliability of the results was verified. Furthermore, the immunological cell profile and SSHL did not appear to be closely associated, as shown by reverse MR analysis.ConclusionOur study provides more support for the current hypothesis that immunophenotypes and the pathophysiology of SSHL are closely associated. Further validation is needed to assess the role of these immunophenotypes in SSHL.

中文翻译：

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免疫细胞表型在特发性突发感音神经性听力损失中的因果作用：双向孟德尔随机化研究

背景越来越多的证据表明，免疫过程在特发性突发感音神经性听力损失（SSHL）的发生中发挥着重要作用。然而，很少有研究使用孟德尔随机化（MR）检查免疫细胞表型和SSHL之间的关联。方法使用在线全基因组关联研究（GWAS）数据库来编译涵盖731种免疫表型和SSHL的GWAS数据。逆方差加权（IVW）分析主要用于MR研究，与免疫表型相关的单核苷酸多态性（SNP）作为因变量。使用敏感性研究和错误发现率 (FDR) 校正来检验 MR 假设。此外，通过反向MR验证了免疫表型和SSHL之间反向因果关系的可能性。反向MR的分析方式与正向MR一致。结果经过FDR校正和敏感性分析，我们筛选了7种免疫表型，包括IgD+CD38暗淡淋巴细胞百分比（95% CI：1.0019、1.0742、p= 3.87 × 10−2，FDR = 1.15 × 10−2）；新南威尔士大学记忆交流 (95% CI: 1.004, 1.2522,p= 4.23 × 10−2，FDR = 2.25 × 10−2）； CD86+骨髓 DC AC（95% CI：1.0083、1.1147、p= 2.24 × 10−2，FDR = 4.27 × 10−2）； CD33暗淡人类白细胞抗原DR-交流（95% CI：1.0046、1.0583、p= 2.12 × 10−2，FDR = 4.69 × 10−2）； CD8 上的 SSC-Abr（95% CI：1.0028、1.1461、p= 4.12 × 10−2，FDR = 4.71 × 10−2）； CD45RA-CD4+%T 细胞（95% CI：1.0036、1.0503、p= 2.32 × 10−2，FDR = 4.82 × 10−2）； DP（CD4+CD8+) AC (95% CI: 1.011, 1.2091,p= 2.78 × 10−2，FDR = 4.97 × 10−2）。与SSHL发病存在很强的因果关系，结果的可靠性得到了验证。此外，如反向MR分析所示，免疫细胞谱和SSHL似乎并不密切相关。结论我们的研究为当前的假设提供了更多支持，即免疫表型和SSHL的病理生理学密切相关。需要进一步验证来评估这些免疫表型在 SSHL 中的作用。