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Molecular subtyping of hypertensive disorders of pregnancy

Author

Listed:
  • Michal A. Elovitz

    (Mirvie Inc.
    Nuttall Women’s Health)

  • Elaine P. S. Gee

    (Mirvie Inc.)

  • Nathaniel Delaney-Busch

    (Mirvie Inc.)

  • Alison B. Moe

    (Mirvie Inc.)

  • Mitsu Reddy

    (Mirvie Inc.)

  • Arkady Khodursky

    (Mirvie Inc.)

  • Johnny La

    (Mirvie Inc.)

  • Ilma Abbas

    (Mirvie Inc.)

  • Kay Mekaru

    (Mirvie Inc.)

  • Hunter Collins

    (Mirvie Inc.)

  • Farooq Siddiqui

    (Mirvie Inc.)

  • Rory Nolan

    (Mirvie Inc.)

  • Rupsa C. Boelig

    (Thomas Jefferson University)

  • Daniel G. Kiefer

    (Women’s Care Florida)

  • Pamela M. Simmons

    (Woman’s Hospital)

  • George R. Saade

    (Eastern Virginia Medical School)

  • Antonio Saad

    (Inova Health)

  • Ebony B. Carter

    (University of North Carolina at Chapel Hill)

  • Thomas F. McElrath

    (Mirvie Inc.
    Brigham Women’s Hospital)

  • Stephen R. Quake

    (Stanford University
    Chan Zuckerberg Biohub
    Stanford University)

  • Mark A. DePristo

    (BigHat Biosciences Inc.)

  • Carrie Haverty

    (Mirvie Inc.)

  • Manfred Lee

    (Mirvie Inc.)

  • Eugeni Namsaraev

    (Mirvie Inc.)

  • Vincenzo Berghella

    (Thomas Jefferson University)

  • Ai-ris Y. Collier

    (Beth Israel Deaconess Medical Center
    Harvard Medical School)

  • Antonia I. Frolova

    (Washington University School of Medicine)

  • Esther Park-Hwang

    (MultiCare Health System)

  • Luis D. Pacheco

    (Univerity of Texas Medical Branch)

  • Elizabeth F. Sutton

    (Woman’s Hospital)

  • Maneesh Jain

    (Mirvie Inc.)

  • Kara Rood

    (The Ohio State University)

  • William A. Grobman

    (The Ohio State University)

  • Joseph R. Biggio

    (Ochsner Health)

  • Cynthia Gyamfi-Bannerman

    (University of California San Diego)

  • Arun Jeyabalan

    (University of Pittsburgh)

  • Morten Rasmussen

    (Mirvie Inc.)

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.

Suggested Citation

  • Michal A. Elovitz & Elaine P. S. Gee & Nathaniel Delaney-Busch & Alison B. Moe & Mitsu Reddy & Arkady Khodursky & Johnny La & Ilma Abbas & Kay Mekaru & Hunter Collins & Farooq Siddiqui & Rory Nolan & , 2025. "Molecular subtyping of hypertensive disorders of pregnancy," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58157-y
    DOI: 10.1038/s41467-025-58157-y
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