lncRNAs与肺腺癌因果关联的两样本孟德尔随机化研究  

A two-sample Mendelian randomized study of causality between lncRNAs and lung adenocarcinoma

作　　者：孙继宏 丛静 王萍玉 SUN Jihong;CONG Jing;WANG Pingyu(Department of Epidemiology,School of Public Health and Management,Binzhou Medical University,Yantai 264003,China;Department of Epidemiology,School of Public Health and Management,Binzhou Medical University,Public Health Division,Yantai Center for Disease Control and Prevention,Yantai 264003,China)

机构地区：[1]滨州医学院公共卫生与管理学院流行病学教研室,烟台264003 [2]滨州医学院公共卫生与管理学院流行病学教研室,烟台市疾病预防控制中心公共卫生科,烟台264003

出　　处：《中华疾病控制杂志》2023年第11期1350-1353,1359,共5页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81772281);山东省自然科学基金(ZR2020KH015)。

摘　　要：目的利用两样本孟德尔随机化方法探究长链非编码RNAs(long-chain non-coding RNAs,lncRNAs)与肺腺癌发病风险之间的因果关联。方法采用肺腺癌全基因组关联分析数据和eQTL Gene联盟的cis-eQTL数据集,将与肺腺癌密切相关的单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为工具变量,运用逆方差加权法、MR-Egger回归模型、加权中位数分析法、简单模式法和加权模式法5种两样本孟德尔随机化(Mendelian randomization,MR)模型来评估lncRNAs与肺腺癌之间的因果效应,并进行异质性检验、基因多效性检验和敏感性分析来评估结果的可靠性和稳定性。结果PVT1、LINC00824、Z94721.1与肺腺癌的关联效应值差异有统计学意义(均P<0.05),PVT1(与肺腺癌的效应值OR=0.79,95%CI:0.71~0.89)、LINC00824(与肺腺癌的效应值OR=0.59,95%CI:0.42~0.83)降低了原发性支气管肺癌(肺癌)的发病风险;而Z94721.1(与肺腺癌的效应值OR=1.09,95%CI:1.03~1.16)增加肺癌的发病风险,并且均通过了异质性检验、基因多效性检验和敏感性分析。结论PVT1、LINC00824、Z94721.13个lncRNAs与肺腺癌之间存在稳定的因果关联,为肺腺癌发病机制的研究提供了重要理论依据。Objective A two-sample Mendelian randomization method was used to investigate the causal relationship between long-chain non-coding RNAs(lncRNAs)and the risk of lung adenocarcinoma.Methods The genome-wide association study data of lung adenocarcinoma and the cis-eQTL data set of eQTL Gene Alliance were used.The single nucleotide polymorphisms(SNPs)closely related to lung adenocarcinoma was used as a tool variable.Five two-sample Mendelian randomization models,including the inverse variance weighting method,MR-Egger regression model,weighted median analysis method,simple mode method and weighted mode method,were applied to evaluate the causal effect between lncRNAs and the risk of lung adenocarcinoma.Moreover,the heterogeneity test,gene pleiotropy test and sensitivity analysis were carried out to evaluate the reliability and stability of the results.Results PVT1,LINC00824,Z94721.1 exhibited significant association with lung adenocarcinoma(all P<0.05).The OR was 0.79(95%CI:0.71-0.89)for PVT1 and 0.59(95%CI:0.42-0.83)for LINC00824,indicating that both PVT1 and LINC00824 reduced the risk of lung cancer.The OR was 1.09(95%CI:1.03-1.16)for Z94721.1,showing that Z94721.1 increased the risk of lung cancer.All passed the heterogeneity test,gene pleiotropy test and sensitivity analysis.Conclusions The three lncRNAs,PVT1,LINC00824 and Z94721.1,have stable causal association with lung adenocarcinoma,providing an important theoretical basis for the study of the pathogenesis of lung adenocarcinoma.

关 键 词：孟德尔随机化 长链非编码RNAs 肺腺癌 因果推断 

分 类 号：R734.2[医药卫生—肿瘤]