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

Abstract

Abstract: 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.

Key words: cognitive performance, chronic heart failure, mendelian randomization, causality, GWAS

CLC Number:

R541
R741

YU De-hua, CHEN Jing-wei. Causal Relationship Between Cognitive Performance and Chronic Heart Failure: A Two-Sample Bidirectional Mendelian Randomization Analysis[J]. ZHONGHUA YANGSHENG BAOJIAN, 2024, 42(19): 8-12.

References

[1] PORSTEINSSON A P, ISAACSON R S, KNOX S, et al.Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021[J].J Prev Alzheimers Dis, 2021,8(3):371-386.
[2] 任汝静,殷鹏,王志会,等.中国阿尔茨海默病报告2021[J].诊断学理论与实践,2021,20(4):317-337.
[3] KARA B, GORDON M N, GIFANI M, et al.Vascular and Nonvascular Mechanisms of Cognitive Impairment and Dementia[J].Clin Geriatr Med,2023,39(1):109-122.
[4] JONGSIRIYANYONG S, LIMPAWATTANA P.Mild Cognitive Impairment in Clinical Practice: A Review Article[J].Am J Alzheimers Dis Other Demen,2018,33(8):500-507.
[5] 中国心血管健康与疾病报告编写组.中国心血管健康与疾病报告2022概要[J].中国循环杂志,2023,38(6):583-612.
[6] ZHANG Y, ZHANG J, BUTLER J, et al.Contemporary Epidemiology, Management, and Outcomes of Patients Hospitalized for Heart Failure in China: Results From the China Heart Failure (China-HF) Registry[J].J Card Fail,2017,23(12):868-875.
[7] WANG H, CHAI K, DU M, et al.Prevalence and Incidence of Heart Failure Among Urban Patients in China: A National Population-Based Analysis[J].Circ Heart Fail,2021,14(10):e008406.
[8] AGARWAL K S, KAZIM R, XU J, et al.Unrecognized Cognitive Impairment and Its Effect on Heart Failure Readmissions of Elderly Adults[J].J Am Geriatr Soc,2016,64(11):2296-2301.
[9] VISHWANATH S, QADERI V, STEVES C J, et al.Cognitive Decline and Risk of Dementia in Individuals With Heart Failure: A Systematic Review and Meta-analysis[J].J Card Fail,2022,28(8):1337-1348.
[10] LAWLOR D A, HARBORD R M, STERNE J A, et al.Mendelian randomization: using genes as instruments for making causal inferences in epidemiology[J].Stat Med,2008,27(8):1133-1163.
[11] LEE J J, WEDOW R, OKBAY A, et al.Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals[J].Nat Genet,2018,50(8):1112-1121.
[12] SAKAUE S, KANAI M, TANIGAWA Y, et al.A cross-population atlas of genetic associations for 220 human phenotypes[J].Nat Genet,2021,53(10):1415-1424.
[13] SEKULA P, DEL GRECO M F, PATTARO C, et al. Mendelian Randomization as an Approach to Assess Causality Using Observational Data[J].J Am Soc Nephrol,2016,27(11):3253-3265.
[14] BURGESS S, DAVEY SMITH G, DAVIES N M, et.al. Theodoratou E. Guidelines for performing Mendelian randomization investigations: update for summer 2023[J].Wellcome Open Res,2023,4:186.
[15] YANG M, XU J, ZHANG F, et al.Large-Scale Genetic Correlation Analysis between Spondyloarthritis and Human Blood Metabolites[J].J Clin Med,2023,12(3):1201.
[16] BURGESS S, THOMPSON S G.CRP CHD Genetics Collaboration. Avoiding bias from weak instruments in Mendelian randomization studies[J].Int J Epidemiol,2011,40(3):755-764.
[17] HARTWIG F P, DAVIES N M, HEMANI G, et al.Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique[J].Int J Epidemiol,2016,5(6):1717-1726.
[18] BURGESS S, FOLEY C N, ZUBER V.Inferring Causal Relationships Between Risk Factors and Outcomes from Genome-Wide Association Study Data[J].Annu Rev Genomics Hum Genet,2018,19:303-327.
[19] BURGESS S, THOMPSON S G.Mendelian Randomization: Methods for Causal Inference Using Genetic Variants (2nd ed.)[M].New York:Chapman and Hall/CRC,2021.
[20] RUSSO C, JIN Z, HOMMA S, et al.Subclinical left ventricular dysfunction and silent cerebrovascular disease: the Cardiovascular Abnormalities and Brain Lesions (CABL) study[J].Circulation,2013,128(10):1105-1111.
[21] JEFFERSON A L, HIMALI J J, BEISER A S, et al.Cardiac index is associated with brain aging: the Framingham Heart Study[J].Circulation,2010,122(7):690-697.
[22] 张紫嫣,郑亮,刘昕雯,等.中国认知障碍患者与心力衰竭发病关系的meta分析[J].上海预防医学,2021,33(4):327-334.
[23] FARLOW MR, HE Y, TEKIN S, et al.Impact of APOE in mild cognitive impairment[J].Neurology,2004,63(10):1898-1901.
[24] 刘颖望,赵水平,聂赛,等.慢性心力衰竭时载脂蛋白E基因多态性[J].中国动脉硬化杂志,2010,18(4):307-310.
[25] 赵郑波. 慢性心力衰竭与认知障碍相关性研究[D].重庆:重庆医科大学,2013.
[26] GÓMEZ-SORIA I, IGUACEL I, AGUILAR-LATORRE A, et al. Cognitive stimulation and cognitive results in older adults: A systematic review and meta-analysis[J].Arch Gerontol Geriatr,2023,104:104807.