Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis

Background Aortic valve stenosis (AVS) is currently the most common heart valve disease. The results of observational studies on the incidence of AVS in the renal dysfunction population are contradictory due to the short follow-up period and different diagnostic criteria, etc. This study aimed to ex...

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Main Authors: Wanqian Pan, Le Zhou, Rui Han, Xiaojiao Du, Weixiang Chen, Tingbo Jiang
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2024.2417742
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author Wanqian Pan
Le Zhou
Rui Han
Xiaojiao Du
Weixiang Chen
Tingbo Jiang
author_facet Wanqian Pan
Le Zhou
Rui Han
Xiaojiao Du
Weixiang Chen
Tingbo Jiang
author_sort Wanqian Pan
collection DOAJ
description Background Aortic valve stenosis (AVS) is currently the most common heart valve disease. The results of observational studies on the incidence of AVS in the renal dysfunction population are contradictory due to the short follow-up period and different diagnostic criteria, etc. This study aimed to explore the causal relationship between kidney function and AVS using Mendelian randomization (MR) analysis.Methods We acquired summary statistics of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) from the CKDGen Consortium and a study on AVS from the FinnGen biobank. Univariate and multivariable MR analyses were conducted to evaluate the causal associations. The MR-Egger intercept and MR-PRESSO Global test were applied to assess the pleiotropic effects. The heterogeneity of MR results was tested by Cochran’s Q statistic. Moreover, the Bonferroni and FDR corrections were performed for multiple tests.Results Genetically predicted decreased eGFR may be associated with a raised risk of AVS (OR = 0.045, p = 1.317e-04 by IVW; OR = 0.002, p = 0.004 by MR-Egger, OR = 0.091, p = 0.057 by WM). The causal association still established after multiple comparisons. Quality control analyses indicated the absence of heterogeneity and pleiotropy in our MR research. In addition, the causality of eGFR and AVS remained significant in multivariable MR analysis after adjusting BMI, hypertension, T2DM, LDL-C, and smoking.Conclusion Our MR study discovered that reduced eGFR may be a causative risk factor for AVS. In addition, the evidence did not support a significant causal association of AVS on kidney function.
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spelling doaj-art-60a5f5c09b964d0997afae4f687576e62025-08-20T02:29:56ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2417742Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysisWanqian Pan0Le Zhou1Rui Han2Xiaojiao Du3Weixiang Chen4Tingbo Jiang5Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Radiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, ChinaDepartment of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, ChinaBackground Aortic valve stenosis (AVS) is currently the most common heart valve disease. The results of observational studies on the incidence of AVS in the renal dysfunction population are contradictory due to the short follow-up period and different diagnostic criteria, etc. This study aimed to explore the causal relationship between kidney function and AVS using Mendelian randomization (MR) analysis.Methods We acquired summary statistics of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) from the CKDGen Consortium and a study on AVS from the FinnGen biobank. Univariate and multivariable MR analyses were conducted to evaluate the causal associations. The MR-Egger intercept and MR-PRESSO Global test were applied to assess the pleiotropic effects. The heterogeneity of MR results was tested by Cochran’s Q statistic. Moreover, the Bonferroni and FDR corrections were performed for multiple tests.Results Genetically predicted decreased eGFR may be associated with a raised risk of AVS (OR = 0.045, p = 1.317e-04 by IVW; OR = 0.002, p = 0.004 by MR-Egger, OR = 0.091, p = 0.057 by WM). The causal association still established after multiple comparisons. Quality control analyses indicated the absence of heterogeneity and pleiotropy in our MR research. In addition, the causality of eGFR and AVS remained significant in multivariable MR analysis after adjusting BMI, hypertension, T2DM, LDL-C, and smoking.Conclusion Our MR study discovered that reduced eGFR may be a causative risk factor for AVS. In addition, the evidence did not support a significant causal association of AVS on kidney function.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2417742Aortic valve stenosischronic kidney diseaseestimated glomerular filtration rategenome-wide association studieskidney functionMendelian randomization
spellingShingle Wanqian Pan
Le Zhou
Rui Han
Xiaojiao Du
Weixiang Chen
Tingbo Jiang
Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
Renal Failure
Aortic valve stenosis
chronic kidney disease
estimated glomerular filtration rate
genome-wide association studies
kidney function
Mendelian randomization
title Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
title_full Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
title_fullStr Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
title_full_unstemmed Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
title_short Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
title_sort causal associations between kidney function and aortic valve stenosis a bidirectional mendelian randomization analysis
topic Aortic valve stenosis
chronic kidney disease
estimated glomerular filtration rate
genome-wide association studies
kidney function
Mendelian randomization
url https://www.tandfonline.com/doi/10.1080/0886022X.2024.2417742
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