Mendelian randomization study on the causal link between reproductive behavior and postpartum depression

This study employed Mendelian randomization (MR) to explore the causal relationships between age at first sexual intercourse (AFS), lifetime number of sexual partners (LNSP), age at first birth (AFB) and risk of postpartum depression (PPD). We used aggregated data from genome-wide association studies to analyze AFS, LNSP, and AFB as exposure variables, with PPD as the outcome variable. Single nucleotide polymorphisms (SNPs) strongly correlated with exposure variables were selected as instrumental variables. MR analysis was conducted using 5 methods: inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted modes. The Cochran's Q test was used to evaluate heterogeneity among SNPs. The MR-Egger intercept method assessed horizontal pleiotropy, whereas leave-one-out analysis evaluated the sensitivity of the causal association. IVW analysis revealed a significant negative causal relationship between AFS and PPD (OR = 0.417, 95% CI: 0.327-0.531, P < .001) and between AFB and PPD (OR = 0.842, 95% CI: 0.762-0.931, P < .001). However, there was a positive causal link between LNSP and PPD (OR = 1.965, 95% CI: 1.202-3.212, P = .007). The Cochran's Q test for the causal link suggested heterogeneity among SNPs between AFS and PPD (P < .05) and LNSP and PPD (P < .05), focusing on the results of IVW. There was no heterogeneity in SNPs between the AFB and PPD groups (P  > .05). The results of the MR-Egger intercept test showed no horizontal pleiotropy, and the leave-one-out analysis confirmed that the 3 causal links were robust. Our study demonstrated that AFS, LNSP, and AFB were causally associated with PPD risk. Early AFB, AFS, and increased LNSP are risk factors for PPD.