The Causation Between Chronic Kidney Disease And Coronary Artery Disease

Traditional observational studies have detected an association between chronic kidney disease(CKD)and coronary artery disease(CAD),but causal relationship is unclear.Two-sample mendelian randomization(TSMR)has the most important advantage is that genes protected before disease and affected less by environment factors,which can make up for the shortcomings of traditional epidemiological studies for the causation of two complex diseases.TSMR is based on the principle of mendelian randomization,using genotype wide association study's(GWAS)summary statistics for the realization of two complex diseases.ObjectiveThis study intends to perform TSMR to explore the causation between CKD and CAD in both positive and negative directions.MethodsFirstly,the data was obtained and prepared.The GWAS database for CKD and CAD was obtained through the publicly available GWAS database,and the data was initially collated.Secondly,according to the three assumptions that Mendelian randomization needs to fulfill,the instrumental variables(IV)are selected and verified.(1)IVs are related to CKD.(2)IVs are not directly related to CAD.(3)the effect of IVs on CAD is only achieved through CKD.Thirdly,TSMR was performed.In this study,the method of inverse variance weighting(IVW)was mainly used for analysis and preliminary analysis results were obtained.Finally,in order to ensure the accuracy of the research results,the study performed quality control on the preliminary analysis results,including IVs' heterogeneity test,sensitivity analysis,other TSMR analysis methods were used to validate the analysis results,andthe bidirectional TSMR was performed to verify the causation between CAD and CKD.ResultsAfter the selection and validation of the IVs,a total of four IVs were selected and finally included in the TSMR analysis.The results of IVW is(OR=1.092,95%CI: 1.014-1.178,P = 0.019<0.05),indicating that CKD is a risk factor for CAD.The results of several other analytical methods were: fixed effect model(OR=1.092,95% CI: 1.014-1.178,P=0.019<0.05),random effects model(OR=1.091,95%CI: 1.013-1.174,P=0.022<0.05),maximum likelihood estimates(OR=1.093,95%CI: 1.015-1.177,P=0.020<0.05)and the bidirectional TSMR(OR=1.044,95%CI: 0.931-1.170,P=0.459>0.05)were consistent with the analysis of IVW,indicating that CKD is a risk factor for CAD.Conclusions1.It is proved that there is a causal relationship between CKD and CAD.The results confirm that CKD is the cause of CAD and CAD is the result of CKD.2.This research method provides detailed research ideas and methods for solving other two complex diseases or traits with the same problem.3.The results of this study provide basic clues and ideas for demonstrating the pathogenesis of CKD and CAD.3.The results of this study provide basic clues and evidence for the basic research on the pathogenesis of CKD and CAD.