Genetic liability to atrial fibrillation, aortic valve disease, and mitral valve disease: a two-sample Mendelian randomization study

BACKGROUND: Research has revealed a relationship between atrial fi brillation (AF) and valvular heart disease; however, the causality remains largely unknown.This study explored whether a causal association between AF and non-rheumatic aortic valve disease (AVD) and mitral valve disease (MVD) could be found. METHODS:A two-sample Mendelian randomization (TSMR) method was applied to determine the causal eff ect of AF on AVD, mitral regurgitation, and MVD.The inverse variance weighted (IVW) method was used as the primary analytical approach, and several complementary analyses were conducted.Outliers were detected using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and radial Mendelian randomization (MR) methods. RESULTS:Genetically predicted AF was found to be causally associated with the risk of MVD (odds ratio [OR]=1.001;95% confi dence interval [CI]: 1.000-1.001;P=1.33×10 -6 ) and mitral regurgitation (OR=1.001;95% CI: 1.000-1.002;P=0.009).However, no signifi cant causal associations between AF and AVD were detected (OR=1.000; 95% CI: 0.999-1.000;P=0.804).Causal eff ects were still detected, even after adjusting for potential risk factors or removing the identifi ed outliers.Reverse MR analyses revealed no signifi cant causal eff ect of valvular heart disease on AF. CONCLUSION:Our findings demonstrate a positive causal association between AF, MVD, and mitral regurgitation, but not AVD.Further research and an aggressive AF management strategy should be explored as potential measures for preventing MVD.