An integrated genome and phenome-wide association study approach to understanding atrial fibrillation’s disease predisposition

Background We performed phenome-wide analysis (PheWAS) and two-sample Mendelian Randomization analysis to comprehensively explore the health effects of atrial fibrillation (AF) in the European population. Methods Initially, SNPs associated with atrial fibrillation were retrieved from the FinnGen database, subsequently compiling a comparative SNP set to serve as a control for PheWAS analysis. A set of unlinked control SNPs (from the 1000 Genomes Project) was generated using SNPsnap. A total of 43 SNPs associated with atrial fibrillation and 172 control SNPs were utilized in the PheWAS analysis, resulting in the identification of 10 associated traits. To evaluate the causal relationship between these associated traits and the risk of AF, a bidirectional two-sample Mendelian randomization analysis was conducted using the TwoSampleMR package (version 0.6.2) in R (version 4.4.0). Results In total, 112 phenotypes with significant associations were identified. Following the False Discovery Rate correction, 5 phenotypes with significant associations were ascertained, each of which demonstrated a causal association with atrial fibrillation as revealed by Mendelian randomization studies Conclusion Overall, our study confirms the association of different factors with genetic susceptibility for AF and reveals novel observations that need to be further explored.