Li Wanqing, Zhou Qiang, Zhou Linsa, Cao Longhe, Zhu Chuansai, Dai Zhijian, Lin Sen
Department of Otolaryngology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Burns and Plastic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Neurol. 2024 Apr 17;15:1368002. doi: 10.3389/fneur.2024.1368002. eCollection 2024.
A 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).
The 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.
After FDR correction and sensitivity analysis, we screened 7 immunophenotypes, including IgD CD38 %lymphocyte (95% CI: 1.0019, 1.0742, = 3.87 × 10, FDR = 1.15 × 10); Unsw mem AC (95% CI: 1.004, 1.2522, = 4.23 × 10, FDR = 2.25 × 10); CD86 myeloid DC AC (95% CI: 1.0083, 1.1147, = 2.24 × 10, FDR = 4.27 × 10); CD33 HLA DR AC (95% CI: 1.0046, 1.0583, = 2.12 × 10, FDR = 4.69 × 10); SSC-A on CD8 (95% CI: 1.0028, 1.1461, = 4.12 × 10, FDR = 4.71 × 10); CD45RA CD4 %T cell (95% CI: 1.0036, 1.0503, = 2.32 × 10, FDR = 4.82 × 10); DP (CD4CD8) AC (95% CI: 1.011, 1.2091, = 2.78 × 10, FDR = 4.97 × 10). 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.
Our 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.
越来越多的证据表明，免疫过程在特发性突发性感音神经性听力损失（SSHL）的发生中起重要作用。然而，很少有研究使用孟德尔随机化（MR）来检验免疫细胞表型与SSHL之间的关联。
利用在线全基因组关联研究（GWAS）数据库，汇总涵盖731种免疫表型和SSHL的GWAS数据。MR研究主要采用逆方差加权（IVW）分析，与免疫表型相关的单核苷酸多态性（SNP）作为因变量。采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验证免疫表型与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。
经过FDR校正和敏感性分析，我们筛选出7种免疫表型，包括IgD CD38 %淋巴细胞（95%可信区间：1.0019，1.0742，P = 3.87×10，FDR = 1.15×10）；Unsw mem AC（95%可信区间：1.004，1.2522，P = 4.23×10，FDR = 2.25×10）；CD86髓样DC AC（95%可信区间：1.0083，1.1147，P = 2.24×10，FDR = 4.27×10）；CD33 HLA DR AC（95%可信区间：1.0046，1.0583，P = 2.12×10，FDR = 4.69×10）；CD8上的SSC-A（95%可信区间：1.0028，1.1461，P = 4.12×10，FDR = 4.71×10）；CD45RA CD4 %T细胞（95%可信区间：1.0036，1.0503，P = 2.32×10，FDR = 4.82×10）；DP（CD4CD8）AC（95%可信区间：1.011，1.2091，P = 2.78×10，FDR = 4.97×10）。它们与SSHL发病存在强因果关系，结果的可靠性得到验证。此外，反向MR分析表明，免疫细胞谱与SSHL似乎没有密切关联。
我们的研究为当前免疫表型与SSHL病理生理学密切相关的假设提供了更多支持。需要进一步验证以评估这些免疫表型在SSHL中的作用。
