Molecular subtyping of hypertensive disorders of pregnancy.
Publication/Presentation Date
4-8-2025
Abstract
Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. These results reclassify HDP clinical phenotypes into two distinct molecular subtypes, placental-associated or immune-associated. Validation performance for placental-associated HDP yields an AUC of 0.88 in the advanced maternal age population without pre-existing high risk factors. Molecular subtypes create new opportunities to apply precision-based medicine in maternal health.
Volume
16
Issue
1
First Page
2948
Last Page
2948
ISSN
2041-1723
Published In/Presented At
Elovitz, M. A., Gee, E. P. S., Delaney-Busch, N., Moe, A. B., Reddy, M., Khodursky, A., La, J., Abbas, I., Mekaru, K., Collins, H., Siddiqui, F., Nolan, R., Boelig, R. C., Kiefer, D. G., Simmons, P. M., Saade, G. R., Saad, A., Carter, E. B., McElrath, T. F., Quake, S. R., … Rasmussen, M. (2025). Molecular subtyping of hypertensive disorders of pregnancy. Nature communications, 16(1), 2948. https://doi.org/10.1038/s41467-025-58157-y
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40199872
Department(s)
Administration and Leadership
Document Type
Article