Causal relationship between gestational diabetes and preeclampsia: A bidirectional mendelian randomization analysis

Abstract

Aims: The study aimed to explore the potential causal link between gestational diabetes mellitus (GDM) and preeclampsia (PE) using a bidirectional mendelian randomization (MR) analysis.

Materials: We conducted a bidirectional MR analysis to investigate the causal relationship between GDM and PE. Data from public genome-wide association studies (GWAS) for GDM and PE were obtained from the FinnGen consortium. Various MR methods were employed, including inverse-variance weighted (IVW), MR-Egger, and sensitivity analyses. Additionally, a knowledge-based approach identified genes underlying this potential connection.

Results: The IVW method revealed a lack of significant association between GDM and PE (OR: 1.04, 95 % CI: 0.96-1.14; p = 0.275). Conversely, IVW analysis indicated a causal connection from PE to GDM (OR: 1.14, 95 % CI: 1.06-1.23; p < 0.001). Molecular pathway analysis identified 20 key genes, including ASAP2, central to the PE-GDM relationship. Tissue enrichment analysis showed pertinent gene expression in significant tissues. Moreover, lower ASAP2 expression was detected in PE patients' placentas.

Conclusions: Our bidirectional MR analysis offers evidence supporting a causal link between PE and GDM, elucidating their interconnected pathogenesis. Genetic and knowledge-based insights facilitate a deeper comprehension of these complex pregnancy complications.

Keywords: Causal relationship; Genetic instruments; Gestational diabetes mellitus; Mendelian randomization; Preeclampsia.