基于双向孟德尔随机化探究15种微量营养素与呼吸道感染疾病的因果关系  

Exploring the causal relationship between 15 micronutrients and respiratory tract infectious diseases based on bidirectional Mendelian randomization

作　　者：魏晨浩 张秀英[2] 张诗瑶 张来 李兆洋 WEI Chenhao;ZHANG Xiuying;ZHANG Shiyao;ZHANG Lai;LI Zhaoyang(The First Clinical College,Liaoning University of Traditional Chinese Medicine,Liaoning Province,Shenyang110847,China;Department of Pediatrics,the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Liaoning Province,Shenyang110032,China)

机构地区：[1]辽宁中医药大学第一临床学院,辽宁沈阳110847 [2]辽宁中医药大学第一附属医院儿科,辽宁沈阳110032

出　　处：《中国医药导报》2024年第30期8-16,共9页China Medical Herald

基　　金：国家自然科学基金面上项目(8197152087)。

摘　　要：目的采用双向孟德尔随机化的方法探究15种微量营养素与呼吸道感染疾病之间的双向因果关系。方法基于大规模的基因关联分析方法,检索中国知网、Pub Med数据库,从IEU Open GWAS数据库中提取暴露和结局数据,其中包括钙、硒、锌等15种微量营养素及所有流感、细菌性肺炎等10种呼吸道感染疾病。在15种微量营养素与10种呼吸道感染疾病之间依次交替作为暴露因素与结局因素进行双向的孟德尔随机化分析,以逆方差加权法(IVW)作为主要的分析方法,利用MR-Egger回归法、加权中位数法、加权模式法和简单模式法对结果进行补充检验分析,随后利用异质性检验、多效性检验、留一法来验证所得数据的可靠性。结果正向孟德尔随机化分析IVW固定效应模型预测硒与细菌性肺炎(OR=1.0577,95%CI:1.0033~1.1150,P=0.0374)、维生素B9与急性上呼吸道感染(OR=1.1781,95%CI:1.0326~1.3441,P=0.0148)及与所有流感(OR=1.5254,95%CI:1.0410~2.2352,P=0.0303)、维生素B12与病毒性肺炎(OR=0.3568,95%CI:0.1645~0.7739,P=0.0091)及与急性上呼吸道感染(OR=0.8774,95%CI:0.7739~0.9947,P=0.0410)、维生素A_(1)与病毒性肺炎(OR=0.3144,95%CI:0.1236~0.7998,P=0.0151)之间均存在潜在的因果关系。在反向孟德尔随机化分析中,IVW分析显示,病毒性肺炎与维生素E(OR=0.9877,95%CI:0.9780~0.9976,P=0.0149)、急性上呼吸道感染与维生素E(OR=0.9641,95%CI:0.9310~0.9985,P=0.0410)、肺炎链球菌肺炎与维生素A_(1)(OR=1.0095,95%CI:1.0004~1.0187,P=0.0400)、所有流感与维生素B12(OR=0.9739,95%CI:0.9523~0.9961,P=0.0213)之间均存在潜在的因果关系;哮喘相关性肺炎与锌(OR=0.7962,95%CI:0.6815~0.9301,P=0.0040)存在强相关。异质性检验、多效性分析、留一法结果显示,除急性上呼吸道感染与维生素E之间存在水平多效性外,其余因果关系均稳健。结论孟德尔随机化结果显示,在15种微量营养素中硒、锌、维生素A_(1)、维生素B9、�Objective To investigate the bidirectional causal relationship between 15 micronutrients and respiratory tract infections by using bidirectional Mendelian randomization.Methods Based on large-scale gene association analysis,the exposure and outcome data of 15 micronutrients such as calcium,selenium,zinc and ten respiratory tract infections such as all influenza and bacterial pneumonia were extracted from IEU Open GWAS database by searching CNKI and PubMed databases.Bidirectional Mendelian randomization analysis was carried out alternately between 15 micronutrients and ten respiratory tract infections as exposure factors and outcome factors.Inverse variance weighting(IVW)was used as the main analysis method,and MR-Egger regression method,weighted median method,weighted model method,and simple model method were used for supplementary test analysis of the results.Then,heterogeneity test,pleiotropy test,and remain-one method were used to verify the reliability of the obtained data.Results The forward Mendelian randomization results showed that the IVW fixed effect model predicted selenium and bacterial pneumonia(OR=1.0577,95%CI:1.0033-1.1150,P=0.0374),vitamin B9 and acute upper respiratory tract infection(OR=1.1781,95%CI:1.0326-1.3441,P=0.0148)and all influenza(OR=1.5254,95%CI:1.0410-2.2352,P=0.0303),vitamin B12 and viral pneumonia(OR=0.3568,95%CI:0.1645-0.7739,P=0.0091)and acute upper respiratory infection(OR=0.8774,95%CI:0.7739-0.9947,P=0.0410),vitamin A_(1)and viral pneumonia(OR=0.3144,95%CI:1.0326-0.7998,P=0.0151)had potential causal relationships.In reverse Mendelian randomization analysis,IVW analysis showed that viral pneumonia and vitamin E(OR=0.9877,95%CI:0.9780-0.9976,P=0.0149),acute upper respiratory tract infection and vitamin E(OR=0.9641,95%CI:0.9310-0.9985,P=0.0410),Streptococcal pneumoniae pneumonia and vitamin A_(1)(OR=1.0095,95%CI:1.0004-1.0187,P=0.0400),all influenza and vitamin B12(OR=0.9739,95%CI:0.9523-0.9961,P=0.0213).Asthma associated pneumonia was strongly associated with zinc(OR=0.7962,95%CI:

关 键 词：微量营养素 呼吸道感染疾病 孟德尔随机化 因果关系 

分 类 号：R737.31[医药卫生—肿瘤]