基于孟德尔随机化方法研究血清尿酸水平与脑小血管病之间的因果关系  

The Causal Relationship between Serum Uric Acid Levels and Cerebral Small Vessel Disease based on Mendelian Randomization Study

作　　者：杜雅明 徐鑫梓 王睿 王俊力[2] 邵卫[2] 陈国华 DU Yaming;XU Xinzi;WANG Rui;WANG Junli;SHAO Wei;CHEN Guohua(Hubei University of Chinese Medicine,Wuhan 430065,China;Wuhan No.1 Hospital,Wuhan 430033,China)

机构地区：[1]湖北中医药大学,武汉430065 [2]武汉市第一医院神经内科,武汉430022

出　　处：《神经损伤与功能重建》2024年第11期621-623,643,共4页Neural Injury and Functional Reconstruction

摘　　要：目的:探究血清尿酸(SUA)水平是否与脑小血管病(CSVD)存在因果关系。方法:从已发表的全基因组关联研究汇总数据获得SUA、腔隙性脑梗死(LI)、白质高信号(WMH)、各向异性分数(FA)和平均弥散率(MD)的数据,筛选出与SUA强相关(F>10)的单核苷酸多态性(SNPs)作为工具变量,用逆方差加权法、MR-Egger、加权中位数法方法进行因果分析,利用MR-Egger截距法和Cochran's Q检验进行异质性和水平多效性检验。结果:逆方差加权法表明SUA与LI(OR=1.086,95%CI 0.959~1.230,P=0.193)、WMH(OR=1.010,95%CI 0.956~1.066,P=0.725)、FA(OR=1.058,95%CI 0.848~1.320,P=0.617)和MD(OR=1.009,95%CI 0.790~1.288,P=0.943)无关,敏感性分析结果显示无异质性和水平多效性。结论:目前MR研究表明SUA水平与CSVD之间不存在因果关系,但仍需规范化、大样本的临床研究和基于大规模GWAS的MR研究更全面评估它们之间的关联性。Objective:To explore whether there is a causal relation between serum uric acid(SUA)levels and cerebral small vessel disease(CSVD).Methods:Data of SUA,lacunar infarction(LI),white matter hyperintensitie(WMH),fractional anisotropy(FA)and mean diffusivity(MD)were obtained from published genome-wide association study.Single nucleotide polymorphisms(SNPs)strongly associated with SUA(F-statistic>10)were selected as instrumental variables,and causal analysis is carried out by inverse variance weighted,MR-Egger,and Weighted median method.Meanwhile,the heterogeneity and horizontal pleiotropic tests were performed using MR-Egger intercept test and Cochran's Q test.Results:Inverse variance weighted showed that SUA was not associated with LI(OR=1.086,95%CI 0.959~1.230,P=0.193),WMH(OR=1.010,95%CI 0.956~1.066,P=0.725),FA(OR=1.058,95%CI 0.848~1.320,P=0.617)and MD(OR=1.009,95%CI 0.790~1.288,P=0.943).Moreover,sensitivity analysis showed no heterogeneity and horizontal pleiotropy.Conclusion:Current MR Studies had shown no causal relationship between SUA and CSVD,but standardized,large-sample clinical studies and large-scale GWAS-based MR Studies are needed to more fully evaluate the association.

关 键 词：孟德尔随机化 尿酸 脑小血管病 腔隙性梗死 白质高信号 

分 类 号：R741[医药卫生—神经病学与精神病学] R743[医药卫生—临床医学]