■越来越多的证据表明,免疫过程在特发性突发性感觉神经性听力损失(SSHL)的发展中起着重要作用。然而,很少有研究使用孟德尔随机化(MR)检查免疫细胞表型与SSHL之间的关联。
■在线全基因组关联研究(GWAS)数据库用于从GWAS收集涵盖731种免疫表型和SSHL的数据。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)校正来检查MR假设。此外,通过反向MR验证了免疫表型与SSHL之间存在反向因果关系的可能性。以与正向MR一致的方式分析反向MR。
■经过FDR校正和灵敏度分析,我们筛选了7种免疫表型,包括IgD+CD38dim%淋巴细胞(95%CI:1.0019,1.0742,p=3.87×10-2,FDR=1.15×10-2);UnswmemAC(95%CI:1.004,1.2522,p=4.23×10-2,FDR=2.25×10-10-10-2,FDR=2.0083(95%CI=1.002)SSHL发病有很强的因果关系,验证了结果的可靠性。此外,免疫细胞谱和SSHL似乎没有密切相关,如反向MR分析所示。
■我们的研究为当前的假设提供了更多的支持,即免疫表型与SSHL的病理生理学密切相关。需要进一步验证以评估这些免疫表型在SSHL中的作用。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: After 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.
UNASSIGNED: 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.