摘要
目的采用两样本双向孟德尔随机化(Mendelian randomization,MR)方法探究慢性鼻窦炎(chronic rhinosinusitis,CRS)与慢性阻塞性肺疾病(慢阻肺)之间是否存在因果关联。方法正向研究从公开的全基因组关联研究数据集中筛选与CRS密切相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,慢阻肺作为结局变量;反向研究则筛选与慢阻肺密切相关的SNP作为工具变量,CRS作为结局变量。运用逆方差加权法(inverse variance weighted,IVW)、MR-Egger回归分析法、加权中位数法(weighted median,WME)3种回归模型进行双向MR分析以评估CRS与慢阻肺之间的因果关系。采用Cochran Q统计、MR-Egger截距项、MR-PRESSO、“留一法”进行异质性和水平多效性检验,以评估MR结果的稳定性和可靠性。结果正向研究共纳入14个与CRS密切相关的SNP。正向研究的固定效应IVW分析结果显示CRS可能会增加慢阻肺的发病风险[比值比(odds ratio,OR)=1.003,95%置信区间(confidence interval,CI)(1.002,1.004),P<0.001],且在WME法中加以证实,而MR-Egger回归分析法则未显示出二者之间的因果关联。异质性检验(IVW结果:Cochran Q=7.910,P=0.849;MR-Egger回归分析法结果:Cochran Q=7.450,P=0.827)、MR-Egger截距法(P=0.510)、MR-PRESSO检验(P=0.917)、“留一法”分析结果均提示MR分析结果具有可靠性。反向研究共纳入12个与慢阻肺相关的SNP作为工具变量,其MR分析结果不支持慢阻肺会增加CRS的发病风险(P>0.05);异质性检验(IVW结果:Cochran Q=5.947,P=0.877;MR-Egger回归分析法结果:5.937,P=0.821)、MR-Egger截距法(P=0.921)、MR-PRESSO检验(P=0.875)、“留一法”分析结果均提示MR分析结果可靠。结论CRS与慢阻肺之间可能存在因果关联,CRS可能会增加慢阻肺的发病风险,但未发现慢阻肺导致CRS风险增加的证据。
Objective To investigate the potential causal relationship between chronic rhinosinusitis(CRS)and chronic obstructive pulmonary disease(COPD)using a two-sample two-way Mendelian randomization(MR)approach.Methods In the forward study,single nucleotide polymorphisms(SNPs)closely associated with CRS were selected as instrumental variables from publicly available genome-wide association studies datasets,with COPD as the outcome variable;conversely,in the reverse study,SNPs closely associated with COPD were selected as instrumental variables,with CRS as the outcome variable.MR analysis was conducted using three regression models:inverse variance weighted(IVW),MR-Egger regression analysis,and weighted median(WME)to assess the causal relationship between CRS and COPD.Cochran’s Q statistic,MR-Egger intercept,MR-PRESSO,and“leave-one-out”methods were employed to test for heterogeneity and horizontal pleiotropy,thereby evaluating the stability and reliability of the MR results.Results A total of 14 SNPs closely associated with CRS were included in the forward study;the IVW-fixed effects analysis indicated that CRS may increase the risk of developing COPD[odds ratio=1.003,95%confidence interval(1.002,1.004),P<0.001],which was confirmed by the WME method,while the MR-Egger regression method did not show a causal link between CRS and COPD.Heterogeneity test(IVW result:Cochran’s Q=7.910,P=0.849;MR-Egger regression result:Cochran’s Q=7.450,P=0.827),MR-Egger intercept method(P=0.510),MR-PRESSO test(P=0.917),and“leave-oneout”method showed that the MR analysis results were reliable.In the reverse study,a total of 12 SNPs related to COPD were included as instrumental variables;MR analysis did not support the notion that COPD would increase the risk of CRS(P>0.05).Heterogeneity test(IVW result:Cochran’s Q=5.947,P=0.877;MR-Egger regression result:Cochran’s Q=5.937,P=0.821),MR-Egger intercept method(P=0.921),MR-PRESSO test(P=0.875),and“leave-one-out”analysis method showed that the MR analysis results were reliable
作者
郭晴晴
牛丁忍
周凌
GUO Qingqing;NIU Dingren;ZHOU Ling(First Clinical Medical College,Heilongjiang University of Chinese Medicine,Harbin 150040,P.R.China;Department of Otorhinolaryngology,the First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,P.R.China)
出处
《华西医学》
CAS
2024年第9期1450-1456,共7页
West China Medical Journal
基金
国家自然科学基金(81874495)
国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函【2022】75号)。
关键词
慢性鼻窦炎
慢性阻塞性肺疾病
孟德尔随机化
因果关联
Chronic rhinosinusitis
chronic obstructive pulmonary disease
Mendelian randomization
causal association
