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.