1型糖尿病与突发性感觉神经性耳聋的风险增加有关:基于两样本孟德尔随机化方法  

Type 1 diabetes mellitus increases the risk of sudden sensorineural hearing loss:A two-sample Mendelian randomization study

作　　者：丁艳[1,2] 张康佳 张勇 伍伟景[1,2] 肖自安 赖若沙[1,2] DING Yan;ZHANG Kangjia;ZHANG Yong;WU Weijing;XIAO Zi’an;LAI Ruosha(Department of Otolaryngology-Head and Neck Surgery,Second Xiangya Hospital,Central South University,Changsha 410011;Clinical Medical Research Center for Otology in Hunan Province,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院耳鼻咽喉头颈外科,长沙410011 [2]湖南省耳科临床医学研究中心,长沙410011

出　　处：《中南大学学报(医学版)》2024年第11期1821-1827,共7页Journal of Central South University :Medical Science

基　　金：湖南省自然科学基金(2023JJ30753);长沙市自然科学基金(kq2208326,kq2208327);湖南创新型省份建设专项(2023SK4030)。

摘　　要：目的:糖尿病与突发性感觉神经性耳聋(sudden sensorineural hearing loss,SSNHL)密切相关,但目前还没有明确证据表明1型糖尿病(type 1 diabetes mellitus,T1DM)和SSNHL之间存在因果关系。本研究旨在从遗传学角度探讨T1DM对SSNHL发生的影响,以期为指导SSNHL的风险预测和治疗提供参考。方法:从公开的全基因组关联分析(genome-wide association study,GWAS)数据中获得与暴露(T1DM)和结局(SSNHL)相关的遗传信息,筛选工具变量,并使用孟德尔随机化(Mendelian randomization,MR)分析探讨T1DM和SSNHL间的因果关联。采用逆方差加权(inverse variance weighted,IVW)作为主要分析方法,MR-Egger、加权中位数、简单模式和加权模式作为IVW的补充方法,并通过Cochran’s Q检验评估所选工具变量效应大小的异质性,MR-PRESSO排除异常值,MR-Egger回归评估水平多效性,留一法分析探讨删除选定的单个单核苷酸多态性(single nucleotide polymorphism,SNP)对总体结果的影响。结果:共筛选得到127个SNPs作为MR分析的工具变量。IVW分析结果显示T1DM与SSNHL之间存在遗传决定的相关性(OR=1.036,95%CI 1.002~1.071,P=0.038)。森林图和散点图显示T1DM和SSNHL之间存在因果关系,T1DM可增加SSNHL的风险。Cochran’s Q检验结果显示SNPs之间的不存在明显异质性(MR-Egger中Q=126.030,P=0.356;IVW中Q=126.450,P=0.373)。漏斗图大致对称,表明选定的IVs主要与暴露相关,而不与其他潜在混淆因素相关。MR-Egger分析的截距项与0之间的差异无统计学意义(P=0.527),提示SNPs之间不存在水平多效性。MR-PRESSO分析未发现异常SNPs(P=0.356)。留一法分析结果显示去除单个SNP后结果保持稳定。结论:两样本MR分析结果支持T1DM患者具有更高的SSNHL发生风险。Objective:Diabetes mellitus is closely associated with sudden sensorineural hearing loss(SSNHL),but no definitive evidence has established a causal relationship between type 1 diabetes mellitus(T1DM)and SSNHL.This study aims to investigate the impact of T1DM on SSNHL from a genetic perspective,providing insights for risk prediction and treatment strategies.Methods:Genetic data related to exposure(T1DM)and outcome(SSNHL)were obtained from publicly available genome-wide association studies(GWAS).Instrumental variables were selected,and Mendelian randomization(MR)analysis was conducted to explore the causal association between T1DM and SSNHL.Inverse variance weighted(IVW)analysis was used as the primary method,with random-effects IVW serving as the main analytical approach.MR-Egger,weighted median,simple mode,and weighted mode analyses were utilized as supplementary methods.Cochran’s Q test was applied to evaluate the heterogeneity of the selected instrumental variables,MR-PRESSO was applied to detect outliers,MR-Egger regression was used to assess horizontal pleiotropy and leave-one-out analysis was conducted to examine the robustness of individual single nucleotide polymorphisms(SNPs)on the overall results.Results:A total of 127 SNPs were selected as instrumental variables for the MR analysis.IVW analysis demonstrated a genetically determined association between T1DM and SSNHL(OR=1.036,95%CI 1.002 to 1.071,P=0.038).Forest plots and scatter plots indicated a causal relationship,suggesting that T1DM increases the risk of SSNHL.Cochran’s Q test demonstrated no significant heterogeneity among SNPs(MR-Egger:Q=126.030,P=0.356;IVW:Q=126.450,P=0.373).The funnel plot appeared symmetrical,indicating that the selected instrumental variables were primarily related to exposure rather than potential confounding factors.The MR-Egger intercept was not significantly different from zero(P=0.527),indicating no evidence of horizontal pleiotropy among the SNPs.MR PRESSO analysis did not identify any outlier SNPs(P=0.356).Leave-one

关 键 词：1型糖尿病 突发性感觉神经性耳聋 孟德尔随机化 因果关系 风险 

分 类 号：R58[医药卫生—内分泌]