Genetically Predicted Atrial Fibrillation and Valvular Heart Disease: A Two-Sample Mendelian Randomization Study.

Background: Previous studies have found atrial fibrillation (AF) is associated with valvular heart disease (VHD). However, whether there is a causal relationship between these two diseases or it is just a result of bias caused by confounding factors is uncertain. This study aims to examine the potential causal association between AF and VHD by using Mendelian randomization. Methods: In order to examine the causal relationship between AF and VHD, we performed a two-sample Mendelian randomization study by collecting exposure and outcome data from genome-wide association study (GWAS) datasets. We utilized data from FinnGen project (FinnGen, 11,258 cases for VHD including rheumatic fever, 3,108 cases for non-rheumatic VHD, and 75,137 cases for participants) and European Bio-informatics Institute database (EBI, 55,114 cases for AF and 482,295 cases for participants). Inverse-variance weighted (IVW), MR-Egger, and weighted median approaches were performed to estimate the causal effect. Results: The Mendelian randomization analysis indicated that AF increased the risk of VHD by all three MR methods [For VHD including rheumatic fever: IVW, odds ratio (OR) = 1.255; 95% confidence interval (CI), 1.191~1.322; Conclusions: Our study provides strong evidence of a causal relationship between AF and VHD. Early intervention for AF patients may reduce the risk of developing into VHD.