广西医学2026，Vol.48Issue(1)：55-69,15.DOI:10.11675/j.issn.0253-4304.2026.01.07
血细胞扰动反应与血管性痴呆的因果关系——双向孟德尔随机化研究
Causality of blood cell perturbation response with vascular dementia:a bidirectional Mendelian randomization study
摘要
Abstract
Objective To explore the causality of blood cell perturbation response with vascular dementia(VAD)based on bidirectional Mendelian randomization(MR)analytic method.Methods Blood cell perturbation response and Genome-wide Association Study data of VAD were retrieved from the database of FinnGen.Blood cell perturbation response and VAD were mutually exposed factors and outcome,and single nucleotide polymorphisms(SNP)related to exposed factors were used as instrumental variables.After screening the instrumental variables,inverse variance weighted method was adopted to be the main method of MR analysis,and bidirectional MR analysis was performed by using MR Egger,weighted median method,simple mode,and weighted mode as supplements.Cochran's Q test was explored to evaluate heterogeneity,intercept term was observed through MR Egger method,horizontal pleiotropy was evaluated by MR-PRESSO,and result stability was conducted using leave-one-out method.Results In the forward MR analysis,results of IVW analysis indicated that neutrophil perturbation response(OR=1.088[95%CI:1.018,1.163],P=0.013)and monocyte perturbation response(OR=1.038[95%CI:1.001,1.076],P=0.044)positively correlated with the occurrence of VAD,with results from the remaining analytical methods largely consistent in direction.Platelet perturbation response negatively correlated with the occurrence of VAD(OR=0.923[95%CI:0.874,0.974],P=0.004),and results from the remaining analytical methods were consistent in direction.In the reverse MR analysis,results of IVW analysis revealed that VAD positively correlated with leukocyte perturbation response(OR=1.154[95%CI:1.020,1.306],P=0.023)and erythrocyte perturbation response(OR=1.215[95%CI:1.034,1.428],P=0.018),with results from the remaining analytical methods also largely consistent in direction.In the bidirectional MR analysis,Cochran's Q test results suggested no heterogeneity between SNP(P>0.05).Funnel plot results also expressed that the distribution of effect size was generally symmetrical.MR Egger intercept tests and MR-PRESSO analysis results indicated no horizontal pleiotropy in this study(P>0.05).Leave-one-out analysis demonstrated stable and reliable causality.Conclusion Neutrophil perturbation response and monocyte perturbation response will increase occurrence risk of VAD,whereas platelet perturbation response exerts protective effect on VAD.Conversely,the occurrence of VAD will intensify leukocyte perturbation response and erythrocyte perturbation response.关键词
血管性痴呆/血细胞扰动反应/孟德尔随机化/因果关系全基因组关联研究Key words
Vascular dementia/Blood cell perturbation response/Mendelian randomization/Genome-wide Association Study分类
医药卫生引用本文复制引用
陈小梅,赵位昆,刘丹丹,刘凤英,曾子峰,刘海洺,石榴..血细胞扰动反应与血管性痴呆的因果关系——双向孟德尔随机化研究[J].广西医学,2026,48(1):55-69,15.基金项目
广西自然科学基金项目(2025GXNSFHA069077) （2025GXNSFHA069077）
广西职业教育教学改革研究项目(GXGZJG2021B127) （GXGZJG2021B127）
广西医科大学"四新"项目(SX202411) （SX202411）
广西壮族自治区中医药管理局自筹经费科研课题(GXZYC20240401) （GXZYC20240401）
广西壮族自治区卫生健康委员会自筹经费科研课题(Z20210872) （Z20210872）
