TY - JOUR
T1 - Disentangling the association between kidney function and atrial fibrillation
T2 - a bidirectional Mendelian randomization study
AU - Geurts, Sven
AU - van der Burgh, Anna C.
AU - Bos, Maxime M.
AU - Ikram, M. Arfan
AU - Stricker, Bruno H.C.
AU - Deckers, Jaap W.
AU - Hoorn, Ewout J.
AU - Chaker, Layal
AU - Kavousi, Maryam
N1 - Funding Information:
This study is supported by the Gender and prevention grant ( 555003017 ) from ZonMw .
Publisher Copyright: © 2022 The Author(s)
PY - 2022/5/15
Y1 - 2022/5/15
N2 - 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-tocreatinine 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, pvalue = 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.
AB - 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-tocreatinine 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, pvalue = 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.
UR - http://www.scopus.com/inward/record.url?scp=85126347112&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2022.03.004
DO - 10.1016/j.ijcard.2022.03.004
M3 - Article
C2 - 35278573
AN - SCOPUS:85126347112
SN - 0167-5273
VL - 355
SP - 15
EP - 22
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -