Vitamin B12 deficiency anaemia and gestational diabetes mellitus: a two-sample Mendelian randomization study

Background: To explore the potential causal relationship between vitamin B12(VitB12) deficiency anaemia and gestational diabetes mellitus(GDM) using a two-sample Mendelian randomization(MR) method. Methods: The VitB12 deficiency anaemia and GDM datasets were obtained from the genome-wide association study (GWAS) database. Instrumental variable (IV) was extracted, and inverse-variance weighted (IVW) was used as the main analysis method. Sensitivity analyses were performed to ensure the robustness of the results. Finally, reverse Mendelian randomization analysis was performed to verify whether there was an association. Results: Five single nucleotide polymorphisms (SNPs) associated with vitamin B12 deficiency anaemia were obtained as instrumental variables(IVs). The IVW results showed that vitamin B12 deficiency anaemia was a risk factor for GDM (OR: 1.21; 95% CI 1.04-1.41; P = 0.016), and the same results were obtained in WME (OR:1.18; 95% CI 1.07-1.30; P = 0.001). The robustness of the results was verified using methods of leave-one-out and MR-Egger regression. Reverse Mendelian randomization analysis showed no statistically significant causal relationship between the two (OR: 1.12; 95% CI 0.98-1.28; P = 0.08). Conclusion: This study used the MR methods to reveal for the first time that vitamin B12 deficiency anaemia is a risk factor for the development of GDM.