Assessment of potential risk factors associated with gestational diabetes mellitus: evidence from a Mendelian randomization study.

ABSTRACT

Background: Previous research on the association between risk factors and gestational diabetes mellitus (GDM) primarily comprises observational studies with inconclusive results. The objective of this study is to investigate the causal relationship between 108 traits and GDM by employing a two-sample Mendelian randomization (MR) analysis to identify potential risk factors of GDM. Methods: We conducted MR analyses to explore the relationships between traits and GDM. The genome-wide association studies (GWAS) for traits were primarily based on data from the UK Biobank (UKBB), while the GWAS for GDM utilized data from FinnGen. We employed a false discovery rate (FDR) of 5% to account for multiple comparisons. Results: The inverse-variance weighted (IVW) method indicated that the genetically predicted 24 risk factors were significantly associated with GDM, such as "Forced expiratory volume in 1-second (FEV1)" (OR=0.76; 95% CI 0.63, 0.92), "Forced vital capacity (FVC)" (OR=0.74; 95% CI 0.64, 0.87), "Usual walking pace" (OR=0.19; 95% CI 0.09, 0.39), "Sex hormone-binding globulin (SHBG)" (OR=0.86; 95% CI 0.78, 0.94). The sensitivity analyses with MR-Egger and weighted median methods indicated consistent results for most of the trats. Conclusion: Our study has uncovered a significant causal relationship between 24 risk factors and GDM. These results offer a new theoretical foundation for preventing or mitigating the risks associated with GDM.