Bipolar disorder (BD) and major depressive disorder (MDD) are the most prevalent mood disorders and cause considerable burden worldwide. Compelling evidence suggests a pronounced overlap between these two disorders in clinical symptoms, treatment strategies, and genetic etiology. Here we leverage a BD GWAS (1822 cases and 4650 controls) and a MDD GWAS (5303 cases and 5337 controls), followed by independent replications, to investigate their shared genetic basis among Han Chinese. We have herein identified a lead SNP rs126277 at the 1q32.2 locus, which also exhibited nominal associations with mood disorders and several relevant sub-clinical phenotypes (e.g., mania) in European populations. Bulk tissue and single-cell eQTL analyses suggest that the risk G-allele of rs126277 predicted lower SYT14 mRNA expression in human brains. We generated mice lacking Syt14 (Syt14