Sehoon Park1,2, Soojin Lee3, Yaerim Kim4, Yeonhee Lee3, Min Woo Kang5, Kwangsoo Kim6, Yong Chul Kim5, Seung Seok Han5,7, Hajeong Lee5,7, Jung Pyo Lee7,8,9, Kwon Wook Joo5,7,8, Chun Soo Lim7,8,9, Yon Su Kim1,5,7,8, Dong Ki Kim5,7,8. 1. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 2. Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do 13574, Korea. 3. Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do 11759, Korea. 4. Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Korea. 5. Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea. 6. Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul 03080, Korea. 7. Kidney Research Institute, Seoul National University, Seoul, Korea. 8. Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea. 9. Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul 07061, Korea.
Abstract
AIMS: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function. METHODS AND RESULTS: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530]. CONCLUSIONS: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function. METHODS AND RESULTS: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530]. CONCLUSIONS: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study. Published on behalf of the European Society of Cardiology. All rights reserved.