认知能力与慢性心力衰竭之间的因果关系:一项两样本双向孟德尔随机化分析

Causal Relationship Between Cognitive Performance and Chronic Heart Failure:A Two-Sample Bidirectional Mendelian Randomization Analysis

目的利用全基因组关联研究(Genome-Wide Association Studies,GWAS)获取汇总数据,采用孟德尔随机化(Mendelian Randomization,MR)方法探究认知表现与慢性心力衰竭之间的因果关系。方法认知能力及慢性心力衰竭的GWAS数据均来自MR Base数据库:(http://app.mrbase.org/),获取暴露及结局的汇总数据后通过关联性分析在暴露数据中挑选工具变量,经剔除连锁不平衡(Linkage Disequilibrium,LD)及弱工具变量后,在PhenoScanner网站(http://www.phenoscanner.medschl.cam.ac.uk/)上去除混杂因素,后通过逆方差加权法(Inverse Variance Weighted,IVW)、MR-egger回归及加权中位数法(Weighted Median)获得本研究的结果,其中逆方差加权法为主要方法,MR-egger回归及加权中位数法为辅助分析方法。最利用Cochran’s Q检验本研究异质性、MR-Egger截距测试数据的多效性,并用留一法对本研究进行敏感性分析。结果经过孟德尔随机化研究发现,认知能力[OR=0.847,95%CI(0.759~0.944)]的提高能够降低发生慢性心力衰竭的风险,但无明显证据表明慢性心力衰竭[OR=0.991,95%CI(0.905~1.086)]的发生会导致认知能力下降。结论通过孟德尔随机化研究发现,认知能力的提高可以降低慢性心力衰竭发生的风险。

Objective Utilize Genome-wide Association Studies(GWAS)summary data to investigate the causal relationship between cognitive performance and chronic heart failure using Mendelian Randomization(MR)method.Methods GWAS data on cognitive ability and chronic heart failure are both from the MR-Base database(http://app.mrbase.org/).After obtaining summary data on exposure and outcome,instrumental variables were selected from the exposure data through correlation analysis,excluding linkage disequilibrium(LD)and weak instrumental variables.Confounding factors were removed on the PhenoScanner website(http://www.phenoscanner.medschl.cam.ac.uk/).The results of this study were obtained using the inverse variance weighted method(IVW),MR-Egger regression,and Weighted Median method,with the inverse variance weighted method as the main method and MR-Egger regression and Weighted Median method as supplementary analytical methods.Cochran's Q test was used to assess heterogeneity in this study,MR-Egger intercept test for pleiotropy,and leave-one-out analysis for sensitivity analysis.Results Through Mendelian Randomization,it was found that an improvement in cognitive ability[OR=0.847,95%CI(0.759~0.944)]could reduce the risk of chronic heart failure,but there was no substantial evidence that the occurrence of chronic heart failure[OR=0.991,95%CI(0.905~1.086)]would lead to decreased cognitive ability.Conclusion Mendelian randomization studies have found that improved cognitive ability can reduce the risk of developing chronic heart failure.