Mendelian randomization analysis of the association between childhood overweight or obesity and gestational diabetes mellitus.

Objective: To investigate the association between childhood overweight or obesity and gestational diabetes mellitus (GDM).

Methods: Data were sourced from the Genome-Wide Association Studies database on childhood body mass index (BMI), with 39 620 samples and 8 173 382 single-nucleotide polymorphisms (SNPs), and GDM, with 143 441 samples, including 12 332 GDM cases and 20 149 608 SNPs. Mendelian randomization (MR) was conducted, including inverse variance weighting (IVW), MR-Egger regression, and the weighted median method. Statistical heterogeneity among SNPs was assessed using Cochran's Q test. MR-Egger's intercept, the MR-Pleiotropy RESidual Sum and Outlier (PRESSO) test, and funnel plots were used to evaluate pleiotropy. The leave-one-out method tested the robustness of the IVW results by excluding individual SNPs.

Results: Fifteen SNPs highly related to childhood BMI were identified. IVW analysis indicated that higher childhood BMI is a significant risk factor for GDM (odds ratio 1.50 [95% confidence interval 1.20-1.87]; p < 0.001). The direction of the β value derived from the weighted median method analysis was consistent with that from the IVW analysis. Cochran's Q test showed statistical heterogeneity among SNPs highly related to childhood BMI (p = 0.001), thus prioritizing IVW analysis results. The MR-Egger regression intercept, MR-PRESSO test, and funnel plot analyses demonstrated no horizontal pleiotropy among SNPs highly related to childhood BMI. The leave-one-out analysis indicated that the MR analysis results were largely unchanged after the exclusion of individual SNPs.

Conclusions: Elevated childhood BMI is associated with an increased risk of developing GDM, underscoring the need to address childhood obesity as a preventive strategy. Effective interventions to reduce childhood obesity could be crucial in mitigating this risk.