Causal Association Between Atrial Fibrillation and Depression: Evidence From Mendelian Randomization Analyses

Background This research assessed the causal influence of atrial fibrillation (AF) on depression. Methods A two-sample Mendelian randomization (MR) approach was utilized along with data from additional databases. A genome-wide association study (GWAS) involving 463,010 participants allowed for the exploration of genetic variations associated with AF. Another GWAS with 215,644 individuals offered insights into the relationship between gene variants and depression. Data on the correlation between gene variants and depression were obtained from another GWAS encompassing 449,414 individuals. Effect sizes were assessed utilizing the inverse-variance weighted technique. Sensitivity analysis was conducted by weighted median, outlier, MR pleiotropy residual sum, weighted mode, and MR-Egger. A meta-analysis of the inverse-variance weighted (IVW) results from the two datasets was conducted. Results A significant association was found between genetically predicted AF and increased incidence of depression using 15 single nucleotide polymorphisms (SNPs) as markers. No evidence of gene pleiotropy was detected, as indicated by MR-Egger. Sensitivity analyses employing alternative Mendelian randomization techniques consistently yielded robust results. The combined odds ratio for depression was estimated at 29.19 (95% CI = 4.43-192.13, P < 0.001). Conclusion This study found a causal relationship between genetically predicted AF and a heightened risk of depression.