Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index:A Mendelian Randomization Study  

作　　者：Hui Zhang Meng Hao Zixin Hu Yi Li Xiaoxi Hu Xiaoyan Jiang Zuyun Liu Xuehui Sun Xiaofeng Wang 

机构地区：[1]Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Fudan University,Shanghai 200433,China [2]Fudan University-the People’s Hospital of Rugao Joint Research Institute of Longevity and Ageing,Rugao 226599,Jiangsu,China [3]Key Laboratory of Arrhythmias of the Ministry of Education of China,Tongji University School of Medicine,Shanghai 200092,China [4]Center for Clinical Big Data and Analytics,Second Affiliated Hospital and Department of Big Data in Health Science,School of Public Health,Zhejiang University School of Medicine,Hangzhou 310030,Zhejiang,China

出　　处：《Phenomics》2022年第6期430-437,共8页表型组学（英文）

基　　金：supported by National Key Research and Development Programme of China(2018YFC2000400,2018YFC2000400-3,2018YFC2002000);Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).

摘　　要：Owing to the susceptibility of conventional observational studies to confounding factors and reverse causation,the causal association between cardiac function and frailty is unclear.We aimed to investigate whether cardiac function has causal effects on frailty.In this study,a two-sample Mendelian randomization(MR)study was conducted using genetic variants associated with cardiac function assessed by magnetic resonance imaging phenotypes as instrumental variables.Genetic variants asso-ciated with cardiac function by magnetic resonance imaging(including seven cardiac function phenotypes)and the frailty index(FI)were obtained from two large genome-wide association studies.MR estimates from each genetic instrument were combined using inverse variance weighted(IVW),weighted median,and MR‒Egger regression methods.We found that the increase in genetically determined stroke volume(beta-0.13,95%CI-0.16 to-0.10,p=1.39E-6),rather than other cardiac phenotypes,was associated with lower FI in MR analysis of IVW after Bonferroni correction.Sensitivity analyses examining potential bias caused by pleiotropy or reverse causality revealed similar findings(e.g.,intercept[SE],-0.008[0.011],p=0.47 by MR‒Egger intercept test).The leave-one-out analysis indicated that the association was not driven by single nucleotide polymorphisms.No evidence of heterogeneity was found among the genetic variants(e.g.,MR‒Egger:Q statistic=14.4,p=0.156).In conclusion,we provided evidence that improved cardiac function could contribute to reducing FI.These findings support the hypothesis that enhancing cardiac function could be an effective prevention strategy for frailty.

关 键 词：Cardiac function FRAILTY Mendelian randomization GENETICS 

分 类 号：R445.2[医药卫生—影像医学与核医学] R541[医药卫生—诊断学]