Objective:This study aims to explore the potential causal relationship between the age at first sexual intercourse (AFS) and the risk of developing bipolar disorder (BD) using the Mendelian Randomization (MR) approach.Methods:This study leverages Genome-Wide Association Studies (GWAS) data from European ancestries, identifying independent genetic loci associated with AFS and BD as instrumental variables. AFS data came from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU), covering 406 457 individuals (AFS1), and the UK Biobank (UKB), with 397 338 individuals (AFS2). Bipolar disorder GWAS data were sourced from the Psychiatric Genomics Consortium (PGC), featuring 20 352 cases and 31 358 controls in 2019 (BD1), and 41 917 cases with 371 549 controls in 2021 (BD2). The causal effects between AFS and BD were assessed using inverse variance weighting (IVW), supplemented by MR-Egger regression, weighted median (WM), Simple Mode and Weighted Mode to ensure result stability. Effect sizes were determined using odds ratio ( OR) and beta coefficient (β). Results:The forward MR analysis revealed a significant causal relationship between earlier AFS and an increased risk of developing BD (IVW: OR=0.69, 95% CI=0.57-0.82, P<0.001). However, the reverse MR analysis did not find a significant effect of BD on the timing of AFS (IVW: β=0.01, 95% CI=-0.01-0.03, P=0.159). Conclusion:There is a causal relationship between the AFS and the risk of developing BD, while the impact of BD on AFS is not significant.