Objective：Studies have shown that there is a significant correlation between depression and gastroesophageal reflux disease（GERD），but the causal relationship between the two and the direction of correlation are not clear. This study aims to explore the bidirectional causal inference between depression and GERD as well as its subtypes and the underlying mechanism of the disease from the genetic level. Methods：Based on the aggregated data of the genome -wide association study（GWAS）of depression，GERD， reflux esophagitis（RE）and non -erosive gastroesophageal reflux disease（NERD），Mendelian randomization was used to explore the independent causal relationship between depression and GERD，RE and NERD. Multiple omics data，such as GWAS and expression quantitative trait loci（eQTL），were integrated to explore the potential pathogenic genes of depression，GERD and its subtypes by summary-data-based Mendelian randomization（SMR）and functional mapping and annotation（FUMA）methods. The potential mechanism of depression affecting GERD and its subtypes was evaluated by enrichment analysis. Results：Depression increased the risk of GERD and NERD，but not RE. GERD，RE，and NERD did not increase the risk of depression. Through SMR and FUMA analysis，the potential susceptibility gene for depression was identified as RPL31P12，and the potential susceptibility gene for GERD was identified as NCSTN. The NERD potential susceptibility gene was SPATS2L. Depression and GERD gene common loci were mainly enriched in T cell receptor signaling pathway，DNA-binding transcription factor activity，and RNA polymerase Ⅱ transcriptional regulation region sequence-specific DNA binding. The depression and NERD gene common loci were mainly enriched in nucleosome assembly，protein and complex subunit assembly，and T cell receptor signaling pathway. Conclusion：Depression may increase the risk of GERD and NERD，and the underlying mechanism may play a role through brain-gut axis，neuroimmune pathway， DNA and RNA transcription and regulation，protein metabolism，etc.