Abstract
Background: Many studies have explored the relationship between education and postpartum depression (PPD), with inconsistent results. Our study is to identify which education-related factors (education attainment, qualifications, cognitive performance) played the predominant role in PPD using Mendelian randomization (MR) analysis. Then, we explored the factors that may mediate the effect of education on PPD. Method: We performed two-sample multivariable Mendelian randomization (MVMR) to assess the independent impact of education-related factors on PPD. Based on the literature review, three mediating factors that may play a role in the path of education attainment and PPD were involved in mediation analysis, including childbearing age, neuroticism score, and average total household income before tax. Then, we used two-step MR and MVMR to estimate the indirect effect of these mediators. Results: We identified genetically predicted 1-SD (3.71 years) higher education attainment (OR: 0.632; [95% confidential interval (CI): 0.464-0.860]); qualifications (OR: 0.418; [95% CI: 0.245-0.714]); or cognitive performance (OR: 0.770; [95% CI: 0.652-0.909]) was associated with lower risk of PPD, and the causal effects of education attainment (OR: 0.407; [95% CI: 0.214-0.773]) on PPD were independent of qualifications and cognition. Childbearing age (β: -0.497; [95% CI: -0.788-0.238]; p < 0.001) and neuroticism score (β: -0.07; [95% CI: -0.120-0.030]; p < 0.001) were identified as mediators of the association between education attainment and PPD. Conclusions: These results suggested the predominant impact of education attainment on PPD independent of qualifications and cognition. Education level mainly affects PPD by changing the childbearing age. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033433.