Blood Pressure Levels During Pregnancy and Gestational Diabetes Mellitus: A Prospective Cohort Study and Mendelian Randomization Analysis

Background: We aimed to investigate the association and causality between blood pressure (BP) during pregnancy and gestational diabetes mellitus (GDM). Methods: In a Chinese birth cohort study, 5,952 participants with repeated measurements of BP were included. Logistic regression models were used to estimate the associations between BP and BP trajectories with the risk of GDM. Polygenic risk scores (PRS) were used in a one-sample Mendelian randomization (MR) analysis conducted on a subset of the cohort. Linkage disequilibrium score regression and a two-sample MR analysis were performed to explore genetic correlation and causal relationship between BP and GDM in both Europeans and East Asians. Results: Elevated first and mean systolic blood pressure (SBP) during pregnancy were both associated with an increased risk of GDM. Individuals with a High-stable SBP trajectory throughout pregnancy had a higher risk of GDM (OR, 1.43[95% CI, 1.07– 1.88]) compared to those with a low-stable SBP trajectory. The top quintile of genetically predicted SBP was associated with an increased risk of GDM compared to the lowest quintile (OR, 1.54[95% CI, 1.05– 2.27]). A modest genetic correlation between SBP and GDM was observed in Europeans ( r g =0.12, p =0.0002). The MR analysis provided consistent evidence for a causal effect of SBP on GDM in Europeans (OR, 1.42[95% CI, 1.12– 1.82]). Conclusion: Our findings highlight the crucial role of elevated SBP in the development of GDM. Further genetic correlation and MR studies provide compelling evidence suggesting a potential causal relationship, thereby enhancing our understanding of the etiology of GDM. Keywords: blood pressure, gestational diabetes mellitus, shared genetics, Mendelian randomization