The relationship between human blood metabolites and preeclampsia-eclampsia: A Mendelian randomization study

Abstract

Preeclampsia and eclampsia are serious complications of pregnancy, leading to high rates of maternal and neonatal mortality. During pregnancy, there are changes in relevant serum metabolites in women. However, it remains unclear if these serum metabolites contribute to the development of associated disorders during pregnancy. Therefore, we conducted a Mendelian randomization study to explore the causal relationship between serum metabolites and preeclampsia and eclampsia. We utilized the inverse variance weighted model as our primary analysis approach. We complemented this with sensitivity analyses, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis, to ensure the robustness of our findings. Furthermore, we conducted linkage disequilibrium score regression, multivariable Mendelian randomization, and metabolic pathway analysis to further explore the genetic data. The Mendelian randomization analysis has identified γ-glutamylglutamine, inosine, and isoleucine 10 metabolites that are significantly associated with preeclampsia, and γ-glutamylglutamine and phenylacetate 8 metabolites that may potentially contribute to the development of eclampsia. Notably, γ-glutamylglutamine has been found to have a causal relationship with both preeclampsia and eclampsia. In the multivariable Mendelian randomization analysis, our research findings suggest that both isoleucine and X-14304–leucylalanine directly impact preeclampsia within the context of amino acids and peptides. Moreover, our observations reveal that carbohydrates can also have a direct effect on preeclampsia. Importantly, it should be emphasized that only 3-lactate in amino acids has been shown to have a direct influence on eclampsia. This research has the potential to enhance our understanding of the biological variances related to disease status, providing a foundation for future investigations.