社会压力与耳鸣发病之间因果关系的孟德尔随机化研究

A Mendelian randomization study on the causal association between social stress and tinnitus onset

目的基于两样本孟德尔随机化方法探讨社会压力与耳鸣发病之间的因果关系。方法从全基因组关联研究(GWAS)数据库中分别获取社会压力、耳鸣相关遗传数据,筛选出相互独立且与社会压力高度相关的单核苷酸多态性(SNP)作为工具变量,以耳鸣作为结局变量。分别采用逆方差加权法(IVW)、加权中位数法和MR-Egger回归法进行孟德尔随机化分析。采用MR-Egger回归法的截距项评估水平多效性,采用Cochran′s Q统计量评估异质性,并采用留一法进行敏感性分析。结果社会压力数据包含459742例样本,耳鸣数据包含117882例样本,共筛选出10个与社会压力密切相关的SNP作为工具变量。随机效应IVW分析结果显示,社会压力与耳鸣发病存在因果效应(OR=1.251,P=0.036)。随机效应IVW、加权中位数法、MR-Egger回归法的分析结果相似(OR=1.251、1.274、1.438),表明社会压力为耳鸣的危险因素,两者之间存在正向因果效应,且结果不存在异质性及多效性。结论社会压力与耳鸣发病存在因果关系,或可为未来耳鸣的临床防治提供新思路。

Objective To explore the causal relationship between social stress and tinnitus onset using a two-sample Mendelian randomization approach.Methods Genetic data pertaining to social stress and tinnitus were extracted from genome-wide association studies(GWAS)databases.Single nucleotide polymorphisms(SNP)that were independent and strongly correlated with social stress were selected as instrumental variables,with tinnitus serving as the outcome variable.Mendelian randomization analyses were performed using inverse-variance weighted(IVW)method,weighted median method,and Mendelian randomization-Egger regression.The intercept term from Mendelian randomization-Egger regression was utilized to assess horizontal pleiotropy,Cochran's Q statistic was employed to evaluate heterogeneity,and leave-one-out analysis was conducted for sensitivity assessment.Results The social stress dataset encompassed 459,742 samples,while the tinnitus dataset comprised 117,882 samples.A total of 10 SNPs tightly associated with social stress were identified as instrumental variables.The analysis results of random-effects inverse variance weighting(IVW),weighted median method,and Mendelian randomization-Egger regression were similar(OR=1.251,1.274,1.438),indicating that social stress was a risk factor for tinnitus,and there was a positive causal effect between them,with no heterogeneity or pleiotropy in the results.Conclusion There is a causal relationship between social stress and tinnitus onset,which may offer novel perspectives for the clinical prevention and treatment of tinnitus in the future.