Causal effect of the age at first birth with depression: a mendelian randomization study.

Background: This study aimed to explore the causal relationship between age at first birth (AFB) and depression.

Methods: Using the univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) methods to examine the potential correlation between age at first birth (AFB) and major depressive disorder and postpartum depression. A public database was used to obtain the genome-wide association studies (GWAS) summary data. We put inverse-variance-weighted (IVW) as the primary method in Mendelian randomization (MR) analysis and used sensitivity analysis to confirm the robustness of our result.

Results: We found a significant causal association between AFB and major depressive disorder by using the IVW algorithm (odd ratio [OR] 0.826; 95% confidence interval [CI] 0.793 - 0.861; P = 4.51 × 10^- 20). MR-Egger, weighted median, simple mode and weighted mode method concluded the same result (P < 0.05). During the sensitivity analysis, the heterogeneity test (Q-value = 55.061, df = 48, P = 2.81 × 10^- 01, I² = 12.82%) and the leave-one-out plot analysis confirmed the stability of the results. The outcomes of the pleiotropy test (MR-Egger intercept = 8.932 × 10^- 3. SE = 6.909 × 10^- 3. P = 2.02 × 10^- 01) and MR_PRESSO global test (P = 2.03 × 10^- 01) indicated there is no pleiotropy.

Conclusion: There is solid evidence that a higher age at first birth is associated with a lower risk of major depressive disorder.