Mediating role of BMI in the causal relationship between sleep apnea syndrome and postpartum depression: a Mendelian randomization study

BACKGROUND: A Mendelian randomization (MR) study was carried out to investigate the causal relationship between sleep apnea syndrome (SAS) and the risk of obstetric disorders occurring, including postpartum depression, and to evaluate the potential mediating effect of an individual's body mass index (BMI). METHODS: Using genome-wide association study (GWAS) summary-level data, we utilized two-sample univariate MR analysis to examine the causal association between SAS and seven obstetric disorders. The causal effects of SAS on the selected disorders were primarily estimated using inverse variance weighting (IVW), supplemented by MR-Egger regression, and weighted median, simple mode, and weighted mode methods. Two-step MR mediation analysis was next conducted to assess whether the BMI mediated the identified associations. Sensitivity analyses were also performed, including MR-PRESSO, the MR-Egger intercept test, and leave-one-out analysis. Potential reverse causation was also evaluated using the MR-Steiger directionality test. RESULTS: = 0.006). No significant causal associations were observed between SAS and the other six obstetric disorders investigated. The two-step MR mediation analysis indicated that an individual's BMI mediated a portion of the total effect of SAS on the risk of developing PPD, specifically 11.7% (indirect effect OR = 1.132, 95% CI: 1.053-1.217). CONCLUSION: This MR study provides evidence that there is a positive causal relationship between SAS and PPD, and suggests that an individual's BMI may partially mediate this link, highlighting the potential role of weight management in strategies to mitigate the risk of PPD in women with SAS, though this hypothesis requires validation in intervention trials.