解放军医学杂志2026，Vol.51Issue(8)：1206-1215,10.DOI:10.11855/j.issn.0577-7402.2056.2026.0608
19种凝血因子表型与神经退行性疾病关联的双向孟德尔随机化研究及表达数量性状位点共定位分析
Bidirectional Mendelian randomization study and expression quantitative trait loci colocalization analysis of the associations between 19 coagulation factor phenotypes and neurodegenerative diseases
摘要
Abstract
Objective To explore the potential causal relationships between 19 coagulation factor phenotypes and 3 common neurodegenerative diseases(NDDs)using a bidirectional two-sample Mendelian randomization(MR)approach.Methods Genome-wide association study(GWAS)data for 19 plasma coagulation factor phenotypes were obtained from the GWAS Catalog database,and genetic data for Alzheimer's disease(AD),Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS)were retrieved from the IEU Open GWAS database.The inverse-variance weighted(IVW)method was used for causal inference,and Cochran's Q test was employed to assess the heterogeneity of single nucleotide polymorphisms(SNPs).To exclude the interference of horizontal pleiotropy,the MR-Egger intercept test was conducted,together with leave-one-out sensitivity analysis and reverse MR validation,to systematically evaluate SNP-specific effects and the stability of the causal direction.Colocalization analysis was subsequently performed to examine the positive SNPs identified in the MR results.Results Plasma coagulation factor ⅩⅢ(F Ⅹ Ⅲ)level(OR=0.951,95%CI 0.925-0.978,P=0.0004),factor Ⅺ(F Ⅺ)level(OR=0.972,95%CI 0.950-0.994,P=0.016),and factor Ⅶ(FⅦ)level(OR=1.024,95%CI 1.001-1.048,P=0.035)were associated with AD.Plasma coagulation factor Ⅴ(FⅤ)level(OR=1.188,95%CI 1.013-1.393,P=0.033)was associated with PD.Plasma vitamin K-dependent protein C level(OR=1.108,95%CI 1.104-1.178,P=0.00084),and activated protein C level(OR=1.149,95%CI 1.034-1.276,P=0.009)were associated with ALS.No horizontal pleiotropy or heterogeneity was detected in any of the above positive results.Colocalization analysis provided moderate evidence for two SNPs(rs11904888,rs8119351),supporting their role as shared genetic factors for the corresponding coagulation factors and NDDs.Reverse MR analysis showed no significant reverse effects of the three NDDs on the respective coagulation factors.Conclusions Higher FⅩⅢ and FⅪ are protective factors for AD,while higher FⅦ is a risk factor for AD;higher FⅤ is a risk factor for PD;higher plasma vitamin K-dependent protein C and activated protein C are risk factors for ALS.关键词
凝血因子/阿尔茨海默病/帕金森病/孟德尔随机化/因果关系Key words
coagulation factors/Alzheimer's disease/Parkinson's disease/Mendelian randomization/causal relationship分类
医药卫生引用本文复制引用
孔涵,姜含笑,贾子璐,程葆华,孔令启..19种凝血因子表型与神经退行性疾病关联的双向孟德尔随机化研究及表达数量性状位点共定位分析[J].解放军医学杂志,2026,51(8):1206-1215,10.基金项目
This work was supported by the National Natural Science Foundation of China(81671276),the Jining Key Research and Development Program(2024YXNS150),and the Innovation and Entrepreneurship Training Program for College Students of Jining Medical University(cx2024213z) 国家自然科学基金(81671276) （81671276）
济宁市重点研发计划(2024YXNS150) （2024YXNS150）
济宁医学院大学生创新创业训练计划(cx2024213z) （cx2024213z）
