Disentangling the association between kidney function and atrial fibrillation: a bidirectional Mendelian randomization study

Sven Geurts; Anna C van der Burgh; Maxime M Bos; M Arfan Ikram; Bruno H C Stricker; Jaap W Deckers; Ewout J Hoorn; Layal Chaker; Maryam Kavousi

doi:10.1016/j.ijcard.2022.03.004

Disentangling the association between kidney function and atrial fibrillation: a bidirectional Mendelian randomization study

Int J Cardiol. 2022 May 15:355:15-22. doi: 10.1016/j.ijcard.2022.03.004. Epub 2022 Mar 9.

Authors

Sven Geurts¹, Anna C van der Burgh², Maxime M Bos¹, M Arfan Ikram¹, Bruno H C Stricker¹, Jaap W Deckers¹, Ewout J Hoorn³, Layal Chaker², Maryam Kavousi⁴

Affiliations

¹ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³ Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.kavousi@erasmusmc.nl.

PMID: 35278573
DOI: 10.1016/j.ijcard.2022.03.004

Abstract

Background: The potential bidirectional causal association between kidney function and atrial fibrillation (AF) remains unclear.

Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis. From multiple genome-wide association studies (GWAS), we retrieved genetic variants associated with kidney function (estimated glomerular filtration rate based on creatinine (eGFRcreat), blood urea nitrogen (BUN), chronic kidney disease (CKD stage ≥G3): n = 1,045,620, eGFR based on cystatin C: n = 24,063-32,861, urine albumin-to-creatinine ratio (UACR), and microalbuminuria: n = 564,257), and AF (n = 1,030,836). The inverse-variance weighted method was used as our main analysis.

Results: MR analyses supported a causal effect of CKD (n = 9 SNPs, odds ratio (OR): 1.10, 95% confidence interval (CI): 1.04-1.17, p-value = 1.97 × 10^-03), and microalbuminuria (n = 5 SNPs, OR: 1.26, 95% CI: 1.10-1.46, p-value = 1.38 × 10^-03) on AF risk. We also observed a causal effect of AF on eGFRcreat (n = 97 SNPs, OR: 1.00, 95% CI: 1.00-1.00, p-value = 6.78 × 10^-03), CKD (n = 107 SNPs, OR: 1.06, 95% CI: 1.03-1.09, p-value = 2.97 × 10^-04), microalbuminuria (n = 83 SNPs, OR: 1.07, 95% CI: 1.04-1.09, p-value = 2.49 × 10^-08), and a suggestive causal effect on eGFRcys (n = 103 SNPs, OR: 0.99, 95% CI: 0.99-1.00, p-value = 4.61 × 10^-02). Sensitivity analyses, including weighted median estimator, MR-Egger, the MR pleiotropy residual sum and outlier test, and excluding genetic variants associated with possible confounders and/or horizontal mediators (myocardial infarction/coronary artery disease, heart failure) indicated that these findings were robust.

Conclusions: Our results supported a bidirectional causal association between kidney function and AF. The shared genetic architecture between kidney dysfunction and AF might represent potential important therapeutic targets to prevent both conditions in the general population.

Keywords: Atrial fibrillation; Chronic kidney disease; Epidemiology; Kidney function; Mendelian randomization; Risk factors.

MeSH terms

Atrial Fibrillation* / diagnosis
Atrial Fibrillation* / epidemiology
Atrial Fibrillation* / genetics
Genome-Wide Association Study
Glomerular Filtration Rate / genetics
Humans
Kidney
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide / genetics