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

Abstract 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. Conclusion 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.