免疫细胞特征与细菌性肺炎风险遗传因果关系的孟德尔随机化研究  

The genetic causal relationship between immunocyte characteristics and the risk of bacterial pneumonia by using Mendelian randomization

作　　者：邓安霞 王子豪 丁芸发 赵翎 李秋林 赵帮豪 胡苏 阿曼古丽·如则 高晓明[1] Deng Anxia;Wang Zihao;Ding Yunfa;Zhao Ling;Li Qiulin;Zhao Banghao;Hu Su;Amanguli Ruze;Gao Xiaoming(State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asian,Cardiology Department of the First Affiliated Hospital of Xinjiang Medical University,Clinical Medical Research Institute of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]省部共建中亚高发病成因与防治国家重点实验室、新疆医科大学第一附属医院心内科、新疆医科大学临床医学研究院、新疆医学动物模型研究重点实验室,新疆乌鲁木齐830054 [2]新疆医科大学第二附属医院神经内科,新疆乌鲁木齐830000 [3]广州中医药大学金沙洲医院甲乳外科,广东广州510168 [4]新疆医科大学第五附属医院心内科,新疆乌鲁木齐830011

出　　处：《中国急救医学》2024年第12期1070-1078,共9页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金资助项目(U1903212);省部共建中亚高发病成因与防治国家重点实验室开放课题项目(SKL-HIDCA-2021-XXG1,SKL-HIDCA-2022-XXG1);新疆重点实验室开放课题项目(2021D04020)。

摘　　要：目的应用孟德尔随机化(Mendelian randomization,MR)技术探究免疫细胞特征与细菌性肺炎之间的相关性。方法选取已知731种免疫细胞特征,从全基因组关联研究(genome-wide association study,GWAS)开放数据库获取数据,使用双样本MR方法揭示免疫细胞特征是否对细菌性肺炎发生风险具有直接影响。两样本MR分析主要采用逆方差加权法(inverse variance weighting,IVW),根据效应指标优势比(OR)和95%置信区间(CI)评估结果,并进行敏感性分析,包括但不限于结果的稳健性验证、潜在的异质性检验以及多效性检验等确保最终结论的科学性及准确性。为避免反向因果关系,将细菌性肺炎作为暴露因素,筛选的六种免疫细胞特征作为结局事件,进行反向MR分析。结果通过MR分析识别出CD33^(-)HLA-DR^(+)髓样细胞、CD86^(+)树突状细胞、CD39^(+)调节性T细胞、HLA-DR^(+)自然杀伤细胞、CD14^(+)CD16^(+)单核细胞及程序性死亡配体1(PD-L1)单核细胞等六种检验效能P<0.01的免疫细胞特征与细菌性肺炎风险存在因果关联。反向MR结果未发现细菌性肺炎与上述六种免疫细胞特征存在因果关系。结论本研究揭示了遗传因素在免疫细胞特征及功能与细菌性肺炎发病风险之间的关系,筛选并鉴定了多种与细菌性肺炎存在显著联系的免疫细胞特征。Objective To investigate the correlation between immunocyte characteristics and bacterial pneumonia by using Mendelian randomization(MR).Methods In this study,731 known immunocyte characteristics were selected from the genome-wide association study(GWAS)open-access database,and a two-sample MR method was used to reveal whether immunocyte characteristics had a direct effect on the risk of bacterial pneumonia.The two-sample MR analysis was mainly performed by using the inverse variance weighting(IVW)method,and the results were assessed based on the odds ratio(OR)and 95%confidence interval(CI)of the effect indicators.In addition,multi-sensitivity analyses including but not limited to robustness validation of the results,potential heterogeneity test and pleiotropy test,were performed to ensure the scientific validity and accuracy of the final conclusions.To prevent reverse causation,bacterial pneumonia was taken as the exposure factor,and the selected six characteristics of immunocytes were taken as the outcome events for a reverse MR analysis.Results MR analysis identified genetic causal relationship between the risk of bacterial pneumonia and the six types of immunocytes characteristics with a test efficacy P<0.01,including CD33^(-)HLA-DR^(+)myeloid cells,CD86^(+)dendritic cells,CD39^(+)regulatory T cells,HLA-DR^(+)natural killer cells,CD14^(+)CD16^(+)monocytes and PD-L1 monocytes.The reverse MR results did not find a causal relationship between the above-mentioned six immunocyte characteristics and bacterial pneumonia.Conclusions This study reveals the role of genetic factors in the relationship of immunocyte type and function with the risk of bacterial pneumonia,and screens and identifies a variety of immunocyte characteristics which are significantly associated with bacterial pneumonia.

关 键 词：细菌性肺炎 免疫细胞特征 孟德尔随机化 全基因组关联研究 逆方差加权法 两样本 双向 

分 类 号：R563.1[医药卫生—呼吸系统]