In conclusion, this study is the first systematic report on the screening and verification of the association of PDE3A and GSK-3β with the risk of atrial fibrillation in the Chinese population, showing that PDE3A is a potential drug target for AF and GSK-3β is a hub gene in the gene–gene network of pathways related to oxidative stress and hormone regulation. Here, GSK3B is linked to atrial fibrillation.