Table_1_Inflammatory markers and the risk of idiopathic sudden sensorineural hearing loss: A Mendelian randomization study.XLS

BackgroundObservational studies suggest that inflammatory markers may increase the risk of idiopathic sudden sensorineural hearing loss (ISSHL). However, the causal relationship between the two has not been established. We sought to assess the possible causal effect between several genetically predicted inflammatory markers and ISSHL by Mendelian random (MR) analysis.
MethodsWe extracted single nucleotide polymorphisms (SNPs) associated with C-reactive protein (CRP), Tumor necrosis factor-α (TNF-α), and fibrinogen from abstract data from the European Individual Large genome-wide association studies (GWAS). Genetic data for ISSHL were obtained from the FinnGen study (n = 196,592). Effect estimates were assessed using inverse variance weighting (IVW) as the primary method. Sensitivity analyses were performed using weighted median, MR-Egger, and MR-PRESSO to evaluate heterogeneity and pleiotropy.
ResultsIn the random-effects IVW approach, there was a significant causal relationship between genetic susceptibility to CRP levels and ISSHL (OR = 1.23, 95% CI = 1.02–1.49, P = 0.03). In contrast, genetic TNF-α and fibrinogen were not risked factors for ISSHL (OR = 1.14, 95% CI = 0.88–1.49, P = 0.30; OR = 0.74, 95% CI = 0.07–7.96, P = 0.30; OR = 1.05, 95% CI = 0.88–1.25, P = 0.59). All the above results were consistent after validation by different Mendelian randomization methods and sensitivity analyses.
ConclusionThis Mendelian randomization study provides causal evidence that CRP is a risk factor for ISSHL, while TNF-α and fibrinogen do not increase the risk for ISSHL Introduction.

**背景** 观察性研究提示，炎症标志物可能升高特发性突发性感音神经性听力损失（idiopathic sudden sensorineural hearing loss, ISSHL）的发病风险，但二者的因果关联尚未明确。本研究拟通过孟德尔随机化（Mendelian random, MR）分析，评估多种经遗传学预测的炎症标志物与ISSHL之间潜在的因果效应。

**方法** 本研究从欧洲大样本全基因组关联研究（genome-wide association studies, GWAS）的摘要数据中，提取与C反应蛋白（C-reactive protein, CRP）、肿瘤坏死因子-α（Tumor necrosis factor-α, TNF-α）及纤维蛋白原相关的单核苷酸多态性（single nucleotide polymorphisms, SNPs）。ISSHL的遗传学数据来自FinnGen研究（样本量n=196592）。以逆方差加权（inverse variance weighting, IVW）法作为主要分析方法评估效应量，并采用加权中位数法、MR-Egger回归及MR-PRESSO检验开展敏感性分析，以评估异质性与多效性。

**结果** 随机效应逆方差加权法分析显示，CRP水平的遗传易感性与ISSHL存在显著因果关联（比值比[OR]=1.23，95%置信区间[95% CI]=1.02~1.49，P=0.03）。与之相反，遗传学预测的TNF-α与纤维蛋白原均未增加ISSHL的发病风险（TNF-α：OR=1.14，95% CI=0.88~1.49，P=0.30；纤维蛋白原：OR=0.74，95% CI=0.07~7.96，P=0.30；另一项指标：OR=1.05，95% CI=0.88~1.25，P=0.59）。经不同孟德尔随机化分析方法及敏感性分析验证后，上述所有结果均保持一致。

**结论** 本孟德尔随机化研究提供了因果证据，表明CRP是ISSHL的危险因素，而TNF-α与纤维蛋白原并未增加ISSHL的发病风险。