Causal associations between vitamin D and postpartum depression: A bidirectional mendelian randomization study

Area of Science:

• Reproductive Health
• Nutritional Psychiatry
• Genetic Epidemiology

Background:

• Observational studies suggest a link between vitamin D and postpartum depression (PPD), but findings are inconsistent.
• A robust investigation into the potential causal relationship between serum 25-hydroxyvitamin D [25(OH)D] and PPD is needed.

Purpose of the Study:

• To investigate the causal relationship between genetically predicted serum 25(OH)D levels and PPD using bidirectional Mendelian Randomization (MR).
• To address inconsistencies in previous epidemiological findings and clarify the role of vitamin D in PPD etiology.

Main Methods:

• Bidirectional Mendelian Randomization (MR) analysis utilizing summary statistics from genome-wide association studies (GWAS).
• Inclusion of large-scale datasets for PPD (15,668 cases, 376,755 controls) and 25(OH)D levels (up to 496,946 participants).
• Primary analysis using inverse-variance weighted (IVW) method, supplemented by MR-Egger and weighted median (WME) methods, with comprehensive sensitivity analyses.

Main Results:

• No significant genetic correlation was found between serum 25(OH)D levels and PPD in either direction.
• Inverse-variance weighted, MR-Egger, and WME analyses consistently showed no causal effect.
• Sensitivity analyses, including leave-one-out tests, confirmed the robustness of the findings, indicating no single SNP unduly influenced the results.

Conclusions:

• The study provides strong evidence against a causal link between vitamin D status and postpartum depression.
• Inconsistencies in prior observational studies are likely attributable to residual confounding, not a direct causal effect.