Mitochondrial Biological Function and Risk of Atrial Fibrillation and Atrial Flutter: A 2-sample Mendelian Randomization Study

Current research suggests that mitochondrial dysfunction can be a contributing factor in the development of cardiac arrhythmias. In pursuit of elucidating the causal link between the biological functions of mitochondria and the occurrence of atrial fibrillation/flutter, we conducted a 2-sample Mendelian randomization (MR) study. Mitochondrial proteins were selected for exposure in this study. To enhance the accuracy of our study, we selected data on AF/AFL from the FinnGen study and the UK Biobank for MR analysis, respectively. The inverse variance-weighted method was utilized as the primary analysis technique for MR. In addition, we performed a series of sensitivity analyses to detect heterogeneity and horizontal pleiotropy. MR results indicated a significant positive association between NAD-dependent protein deacylase sirtuin-5 and AF/AFL (odds ratio = 1.084, 95% confidence interval: 1.037-1.133, P = 3.679 × 10-4, Adjusted P = .024), with consistent outcomes observed in replication analysis (odds ratio = 1.002, 95% confidence interval: 1.001-1.003, P = 4.808 × 10-4, Adjusted P = .032). NAD-dependent protein deacylase sirtuin-5 can significantly promote the occurrence of AF/AFL, and its specific mechanisms warrant further investigation.