A Mendelian Randomization Study on the Causal Relationship between Body Mass Index and Gestational Diabetes Mellitus

SHEN Yi; ZHU Lijuan; DONG Song; LIU Jia; LI Xiaojing; DU Yangfan; LIU Hongzhou; WANG Juan; WANG Linlin

doi:10.3639/j.issn.2095-3097.2025.05.032

Abstract：Objective To investigate the causal relationship between body mass index(BMI)and gestational diabetes mellitus(GDM).Methods A Mendelian randomization(MR)study was conducted.Single nucleotide polymorphisms(SNPs)associated with GDM were selected from genome-wide association studies(GWAS)data as instrumental variables.MR-Egger regression,inverse variance weighted(IVW)method,weighted median method,and weighted mode method were applied to de-termine the causal relationship between BMI and GDM.The strength of association was evaluated using odds ratios(OR)and 95%confidence intervals(95%CI).MR-Egger regression was used to assess heterogeneity and horizontal pleiotropy among SNPs,while leave-one-out analysis was performed for sensitivity analysis.A forest plot was used to analyze the association between each SNP and GDM,and a funnel plot was used to assess the symmetry of SNP distribution.Results Based on the three core assumptions of MR,106 SNPs were included in the analysis.The IVW method showed that increased BMI was as-sociated with approximately a 50.6%higher risk of GDM(OR=1.506,95%CI:1.260-1.751,P<0.001).Heterogeneity testing revealed significant heterogeneity among SNPs(Q=203.2,P<0.001),while the MR-Egger intercept test suggested no evidence of horizontal pleiotropy(intercept=-0.008 6,P=0.265).Leave-one-out analysis indicated that no single SNP had a substantial influence on the overall result.The funnel plot showed symmetrical distribution of SNPs,indicating result stability.Conclusion Mendelian randomization analysis suggests that increased BMI may elevate the risk of developing GDM.Conclusion Con-trast-enhanced ultrasound combined with elastography has strong accuracy in the differential diagnosis of benign and malignant breast nodules,and has high qualitative and quantitative diagnostic efficiency,and can provide a reliable basis for diagnosis and treatment decisions.