Causal association between gestational diabetes mellitus and peripartum mental disorders: Evidence from two-sample Mendelian randomization

Gestational diabetes mellitus (GDM) is associated with multiple maternal and neonatal complications, but its direct causal impact on peripartum mental health remains uncertain. This study used a two-sample Mendelian randomization (MR) approach to assess whether genetically predicted GDM increases the risk of peripartum mental disorders, including depression, anxiety, and suicidality. Genetic variants associated with GDM were obtained from the FinnGen consortium, and summary data for peripartum mental disorders were derived from genome-wide association studies. Independent single-nucleotide polymorphisms (P < 5 × 10-6, r2 < 0.001) were analyzed using inverse-variance weighted, MR-Egger, and weighted median methods. Heterogeneity, pleiotropy, and causal direction were evaluated using Cochran's Q, the MR-Egger intercept, and Steiger filtering. Nineteen independent single-nucleotide polymorphisms were identified. Inverse-variance weighted analysis indicated a positive causal association between genetically predicted GDM and peripartum mental disorders. The estimated effect was β = 0.048, with a standard error (SE) of 0.014 and P = 8.3 × 10⁻⁴; the odds ratio was 1.049 (95% confidence interval = 1.020-1.0779). The results were consistent in all the sensitivity analyses, with no evidence of heterogeneity or pleiotropy. The MR findings provide genetic evidence supporting a causal link between GDM and peripartum mental disorders. These results underscore the need for integrated clinical management that simultaneously addresses metabolic control and psychological well-being in women diagnosed with GDM.