东亚人群心房颤动和心力衰竭的双样本孟德尔随机化研究

A Two Sample Mendelian randomization Randomized Study of Atrial fibrillation and Heart Failure in East Asian Population

目的在观察性研究中心房颤动和心力衰竭有关,进行双样本孟德尔随机化分析,确定这些关联是否具有因果关系。方法单核苷酸多态性(P<5×10^(-8))被用作心房颤动和心力衰竭的工具变量。心房颤动和心力衰竭的遗传关联估计数来自日本生物样本库。采用MR-Egger回归、加权中位数法(weight medianestimator,WME)、逆方差加权法(inverse-varianceweighted,IVW)、简单模型、加权模型进行分析。结果基因预测的心房颤动与心力衰竭具有高度的因果关联。孟德尔随机化结果显示,心房颤动导致心力衰竭的增加,OR为1.14(95%CI:1.10~1.17,P=0.34×10^(9)),异质性检验结果P=0.24。结论本研究提供了心房颤动与心力衰竭风险增加之间因果关系的证据,但具体生物学机制还需进一步研究。

Objective Atrial fibrillation has been associated with heart failure in observational studies.We performed a two-sample Mendelian randomization analysis to determine whether these associations were causal.Methods Single nucleotide polymorphisms(P<5×10^(-8))were instrumental variables for atrial fibrillation and heart failure.Genetic association estimates for atrial fibrillation and heart failure were obtained from the Japan Biobank.MR-Egger regression,weighted median method(weight median estimator,WME),inverse variance weighted method(inverse-variance weighted,IVW),simple model,and weighted model were used for analysis.Results Genetically predicted atrial fibrillation was highly causally associated with heart failure.The results of Mendelian randomization showed that atrial fibrillation led to an increase in heart failure,the OR was 1.14(95%CI:1.10~1.17,P=0.34×10^(9)),and the heterogeneity test result P=0.24.Conclusions This study provides evidence of a causal relationship between AF and increased risk of heart failure,but the specific biological mechanisms require further investigation.