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

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

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.

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.

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