Causal relationship between citrate and gestational diabetes mellitus: a two-sample Mendelian randomization analysis.

Background: Diabetes Mellitus (GDM) is a common metabolic disease during pregnancy, mainly manifested as impaired glucose tolerance in the middle and late stages of pregnancy. As a key intermediate product in the tricarboxylic acid cycle, citrate has been widely recognized for its role in regulating blood glucose levels. However, the potential association between citrate and impaired glucose tolerance during pregnancy needs further research, The aim of this study is to investigate the relationship between citrate levels in the human body and the incidence of gestational diabetes mellitus.

Method: This study adopts a two-sample Mendelian randomization approach, using genetic variants of citrate as instrumental variables, to investigate the causal relationship between citrate and gestational diabetes mellitus (GDM). The research data is derived from the OpenGWAS and FinnGen databases, with single nucleotide polymorphisms (SNPs) related to citrate levels and the incidence of GDM selected as analytical tools. Citrate is designated as the exposure factor, and GDM as the outcome variable. Comprehensive assessments of the causal relationship between the instrumental variables and GDM are conducted using methods such as Inverse Variance Weighted (IVW), MR Egger, Simple Mode, Weighted Median, and Weighted Mode. Additionally, Cochran's Q and I^2 statistics are utilized to evaluate heterogeneity, with visualization provided through funnel plots. To test the robustness of the results, a leave-one-out sensitivity analysis method is employed. Furthermore, the potential pleiotropy in this study is detected using MR Egger.

Result: In this study, a total of 6 SNPs related to citrate were included. The MR causal analysis revealed that the relevant genes of citrate had a significant impact on gestational diabetes mellitus in both the Inverse Variance Weighted method (OR = 0.170, 95% CI: 0.032 to 0.896, p = 0.037) and the Weighted Median method (OR = 0.116, 95% CI: 0.016 to 0.844, p = 0.033). The tests for heterogeneity, pleiotropy, and sensitivity used in this experiment all indicated that there were no special interfering factors in this experiment.

Conclusion: This study found that there is a negative correlation between the level of citrate in pregnant women and gestational diabetes mellitus.