摘要
目的:采用两样本孟德尔随机化(MR)分析研究2型糖尿病(T2DM)和体质指数(BMI)与帕金森病(PD)的因果关联,为早期预防PD、改善预后提供参考。方法:T2DM、BMI和PD的全基因组关联研究(GWAS)汇总数据集来自IEU Open GWAS数据库。选择与T2DM、BMI密切相关的单核苷酸多态性(SNPs)作为工具变量(IVs),回文SNPs和异常SNPs被排除在外,以逆方差加权(IVW)法为主要分析方法估计T2DM和BMI与PD之间的因果关系,MR-Egger回归、加权中位数和加权模型作为补充,以确保结果的准确性。Cochran Q用于检验IVs的异质性,采用MR-Egger-intercept检验水平多效性,通过MR-PRESSO检测异常值,使用留一敏感性检验探讨单个SNP对结果的影响。MR Steiger检验用于分析暴露与结果之间的反向因果。结果:筛选得到61个与T2DM、275个与BMI密切相关的SNPs作为IVs。随机效应IVW的结果表明,遗传预测的T2DM可增加PD的发病风险(OR=1.09,95%CI:1.00~1.20,P=0.047),BMI与PD发病率降低相关(OR=0.83,95%CI:0.72~0.96,P=0.013)。敏感性分析结果表明,用于MR分析的SNPs不存在异质性(P>0.05)和水平多效性(P>0.05);留一敏感性检验表明,没有单个SNP偏向于或依赖于因果关系的情况。MR Steiger检验结果显示,T2DM和BMI与PD间不存在反向因果关联。结论:T2DM、BMI与PD间存在因果关联,T2DM可能是PD的潜在危险因素,而较高的BMI可能有助于降低PD的发生,这一发现可为探索PD的潜在风险因素及制定预防策略提供参考。
Objective:A two-sample Mendelian randomization(MR)analysis was used to study the causal associations of type 2 diabetes mellitus(T2DM)and body mass index(BMI)disease with Parkinson s disease(PD)for early prevention of PD and improvement of disease prognosis.Methods:Genome-wide association study(GWAS)pooled datasets for T2DM,BMI and PD were obtained from the IEU Open GWAS database.Single nucleotide polymorphisms(SNPs)closely associated with T2DM and BMI were selected as instrumental variables(IVs),palindromic SNPs and aberrant SNPs were excluded,and the inverse variance weighting(IVW)method was used as the main analytical method for estimating the causal relationship between T2DM and BMI and PD,and the MR-Egger regression,weighted median,and weighted modeling were used as supplements to ensure that results were accuracy.Cochran Q was used to test for heterogeneity of IVs,MR-Egger-intercept was used to test for horizontal pleiotropy,outliers were detected by MR-PRESSO,and leave-one-out sensitivity analysis was used to explore the effect of individual SNPs on the results.The MR Steiger test was used to analyze reverse causality between exposure and outcome.Results:61 SNPs strongly associated with T2DM and 275 SNPs strongly associated with BMI were screened and obtained as IVs.The results of the random-effects IVW showed that genetically predicted T2DM increased the risk of developing PD(OR=1.09,95%CI:1.00-1.20,P=0.047),and that body mass index(BMI)was associated with a reduced incidence of PD(OR=0.83,95%CI:0.72-0.96,P=0.013).The results of sensitivity analyses showed that there was no heterogeneity(P>0.05)or horizontal pleiotropy(P>0.05)in the SNPs used for MR analysis,and leave-one-out analysis showed that there were no individual SNPs biased toward or dependent on causality.The results of the MR Steiger test showed that there were no inverse causal associations between T2DM,BMI and PD.Conclusion:There is a causal association between T2DM,BMI and PD.T2DM may be a potential risk factor for PD,and a higher BMI may help reduce the occurrence of PD.This finding can provide a reference for exploring potential risk factors for PD and formulating prevention strategies.
作者
姚玲
张庆子
成龙
李海荣
YAO Ling;ZHANG Qingzi;CHENG Long;LI Hairong(Department of Neurology,Xianyang Hospital,Yan an University,Xianyang 712000,China)
出处
《现代医学》
2024年第8期1151-1158,共8页
Modern Medical Journal
基金
陕西省重点研发计划(2023-YBSF-636)
咸阳市重点研发计划(L2023-ZDYF-SF-071)。
关键词
2型糖尿病
体质指数
帕金森病
孟德尔随机化
type 2 diabetes
body mass index
Parkinson s disease
Mendelian randomization
