【摘要】 目的 基于孟德尔随机化方法（MR）分析遗传预测的虚弱指数（FI）与脑卒中的相关性。方法 从一项大型全基因组关联研究（GWAS）中获得与FI相关的工具变量（IVs）。主要采用逆方差加权法估计因果效应，应用多因素MR分析来消除身体质量指数（BMI）、炎症性肠病（IBD）、C-反应蛋白（CRP）对结局的影响，以评估FI和脑卒中的独立因果效应。结果 MR结果表明，遗传预测的FI与脑卒中的高风险之间存在关联（OR=1.360,95%CI:1.006～1.838,P=0.046）。对于卒中亚型，基因预测的FI与大动脉粥样硬化卒中（LAS）的高风险相关（OR=2.482,95%CI:1.279～4.816,P=0.007）。遗传预测的FI与急性脑卒中、非创伤性脑出血卒中、心源性卒中和小动脉卒中之间没有因果关系。多变量MR分析显示，在调整炎症性肠病后，遗传预测的FI与大动脉粥样硬化性脑卒中（LAS）的相关性减弱（P=0.114）。结论MR研究表明，基因预测的FI与脑卒中密切相关。亚组分析表明，基因预测的FI与LAS之间存在相关性，而与IS、CES、SAS及ICH之间没有因果关系。更多还原

【Abstract】 Objective To analyze the correlation between genetic prediction of frailty index(FI) and stroke using Mendelian randomization method(MR).Methods Instrumental variables(IVs) associated with flimsy index(FI) were obtained from a large genome-wide association study(GWAS).Inverse variance weighting was used to estimate the causal effect,and multi-factor MR Analysis was used to eliminate the effects of body mass index(BMI),inflammatory bowel disease,and C-reactive protein on outcomes to evaluate the independent causal effect of FI and stroke.Results MR Results showed an association between genetically predicted FI and a higher risk of any stroke(OR=1.360,95%CI:1.006-1.838,P=0.046).For stroke subtypes,gene-predicted FI was associated with a higher risk of large atherosclerotic stroke(LAS,OR=2.482,95%CI:1.279-4.816,P=0.007).There was no causal relationship between genetically predicted FI and ischemic stroke,intracranial hemorrhage,cardiac embolic stroke,and small artery stroke.Multivariate MR Analysis showed that after adjusting for IBD,the association between genetically predicted FI and large atherosclerotic stroke(LAS) was weakened(P=0.114).Conclusion MR Studies show that gene predicted FI is closely related to stroke.Subgroup analysis showed that gene predicted FI was correlated with LAS,but not with IS,CES,SAS,and ICH.更多还原