摘要
目的运用双样本孟德尔随机化(mendelian randomization,MR)方法探讨731种免疫细胞与骨髓增生异常综合征(MDS)发病风险的潜在因果关系。方法研究数据来源于欧洲3757例个体的免疫细胞特征全基因组关联研究(GWAS)汇总统计数据,以及FinnGen数据库中1018例欧洲MDS患者和342243例对照的基因组数据。采用双样本MR方法估计因果效应,包括逆方差加权法(inverse-variance weighting,IVW)、MR-Egger回归、加权中位数法、简单模式和加权模式法。结果研究发现7种与MDS风险显著相关的免疫细胞特征:HLA-DR^(+)T细胞的前向散射光(forward scatter,FSC)(OR=0.858,P_(FDR)=0.029)和CD11b on CD66^(++)髓系细胞(OR=0.737,P_(FDR)=0.020)为保护性因素。CD33^(+)HLA-DR^(+)CD14^(dim)%CD33^(+)HLA-DR^(+)(OR=1.549,P_(FDR)<0.001)、CD14^(-)CD16^(+)单核细胞计数(OR=1.430,P_(FDR)=0.016)、CD45 on HLA-DR^(+)CD4^(+)T细胞(OR=1.449,P_(FDR)<0.001)、CD33 on CD33^(+)HLA-DR^(+)CD14^(-)(OR=1.176,P_(FDR)=0.034)及CD80 on髓系树突状细胞(OR=1.302,P_(FDR)=0.015)为危险因素。结论特定免疫细胞可能在MDS发病过程中发挥正向或负向调控作用,为MDS发病机制和潜在干预靶点的发现提供了新线索。
Objective This study aimed to evaluate the potential causal relationships between 731 immune cell traits and MDS using a two-sample Mendelian randomization(MR)approach.Methods We utilized summary statistics from genome-wide association studies(GWAS)on immune traits involving 3757 European individuals and MDS dataset from the FinnGen cohort,which included 1018 European patients with MDS and 342243 controls.The primary MR analysis was carried out using the inverse-variance weighted(IVW)method,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included MR-Egger intercept test,leave-one-out analysis,Cochran’s Q test,and MR-PRESSO for pleiotropy detection.Results Our analysis identified two immune cell traits associated with a reduced risk of MDS:FSC on HLA-DR^(+)T cells(OR=0.858;P_(FDR)=0.029)and CD11b on CD66++myeloid cells(OR=0.737:P_(FDR)=0.020).Conversely,five immune cell traits were associated with an increased risk of MDS,including CD33^(+)HLA-DR^(+)CD14^(dim)%CD33^(+)HLA-DR^(+)(OR=1.549;P_(FDR)<0.001),CD14^(-)CD16^(+)monocyte count(OR=1.430;P_(FDR)=0.016),CD45 on HLA-DR^(+)CD4^(+)T cell(OR=1.449;P_(FDR)<0.001),CD33 on CD33^(+)HLA-DR^(+)CD14^(-)(OR=1.176;P_(FDR)=0.034),and CD80 on myeloid dendritic cell(OR=1.302:P_(FDR)=0.015).Conclusion These results suggest that specific immune cell traits could have protective or deleterious roles in the development of MDS.Future research should focus on elucidating the biological mechanisms underlying these associations and exploring potential therapeutic targets to regulate immune cell function in MDS patients.
作者
郜伟峰
张越
单志娟
杨玉
侯艳军
裴新蕊
周合冰
GAO Weifeng;ZHANG Yue;SHAN Zhijuan;YANG Yu;HOU Yanjun;PEI Xinrui;ZHOU Hebing(Department of Hematology,Beijing Luhe Hospital,Capital Medical University,Beijing 101149,China)
出处
《标记免疫分析与临床》
2025年第7期1486-1491,1499,共7页
Labeled Immunoassays and Clinical Medicine
基金
北京市通州区科技计划项目项目(编号:KJ2022CX034)。
关键词
骨髓增生异常综合征
免疫细胞
因果关系
孟德尔随机化
Myelodysplastic syndrome
Immunophenotypes
Causal inference
Mendelian randomization
Sensitivity analyses
