The correlation between Alzheimer's disease and Parkinson's disease based on Mendelian randomization
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NETL
NSTL
万方数据
目的:基于双向孟德尔随机化(MR)方法探究阿尔茨海默病(AD)和帕金森病(PD)之间的相关性,为日后进行性神经退行性疾病的研究和治疗提供参考方向.方法:对 AD 和 PD2 个全基因组关联研究(GWAS)的汇总数据进行分析,利用两组数据显著相关的单核苷酸多态性(SNP)位点作为工具变量,所选用的GWAS数据均来源于欧洲人群.双向MR研究中采用逆方差加权法(IVW)、MR-Egger回归和加权中位数法进行分析评估两疾病的发病关联.经筛选后,最终以与 AD 相关的 4 个 SNP 作为工具变量,PD 为研究结局进行正向MR分析;以与PD相关的 17 个SNP作为工具变量,AD作为研究结局进行反向 MR 分析.运用留一法、MR-Egger截距、离群值(PRESSO)对评估结果进行敏感性分析以确定多效性和单个 SNP 对相关性的影响程度.以比值比(OR)评价AD与PD的因果效应.结果:正向MR 分析结果显示,差异无统计学意义(IVW:OR=0.000 6,95%CI 2.640 1×10-10～1 476.367 4,P=0.324);反向MR分析结果显示,差异无统计学意义(IVW:OR=1.000 3,95%CI 0.999 9～1.000 6,P=0.072).IVW显示AD和PD之间不存在相关性(P＞0.05).Q 检验及 MR-Egger 回归结果表明,AD 和 PD 不存在异质性及基因的水平多效性(P＞0.05).结论:基于基因组水平上SNP研究分析,目前MR研究不支持 AD 与 PD 存在显著的因果关联,仍需要进一步的研究来更全面地评估它们之间的相关性.
Objective:To explore the correlation between Alzheimer's disease(AD)and Parkinson's disease(PD)based on bidirectional Mendelian randomization(MR)and also to provide a reference point for future research and treatment of progressive neurodegenerative diseases.Methods:The pooled data of two genome-wide association studies(GWAS)for AD and PD were analyzed using single nucleotide polymorphism(SNP)with significant correlation between the two data sets of data as instrumental variables.The selected GWAS data were all from European populations.In this bidirectional MR study,inverse variance weighted(IVW),MR-Egger and weighted median(WM)were used to analyze and evaluate the correlation between the two diseases.After screening,forward MR analyses were conducted using 4 SNP associated with AD as instrumental variables and PD as the study outcome.Then reverse MR analyses were conducted using 17 SNP associated with PD as instrumental variables and AD as the study outcome.Sensitivity analyses of the evaluation results were performed using"leave-one-out",MR-Egger intercept,and MR PRESSO to determine the extent to which multiplicity of effects and individual SNP influence correlations.The correlation between AD and PD was evaluated by odds ratio(OR).Results:The results of forward MR analyses showed that the OR obtained by IVW was 0.000 6,95%CI 2.640 1×10-10-1 476.367 4,the difference result was not statistically significant(P=0.324).The results of reverse MR analyses showed that the OR obtained by IVW was 1.000 3,95%CI 0.999 9～1.000 6,and the difference result was not statistically significant(P=0.072).IVW showed no significant correlation between AD and PD(P＞0.05).The results of Cochran Q and MR-Egger showed that there was no heterogeneity or horizontal pleiotropy of genes between AD and PD(P＞0.05).Conclusion:Based on the analyses of SNP studies at the genomic level,the current MR study does not support the existence of a significant causal correlation between AD and PD,and further studies are still needed to evaluate the correlation between them more comprehensively.
NETL
NSTL
万方数据
