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Polygenic Risk Scores for Preeclampsia Prediction Beyond Gold-Standard Clinical Models in Multiethnic Populations.

Maddalena Ardissino1,2,3,4, Kypros Nicolaides4,5, Frances Conti-Ramsden4

  • 1Medical Research Council, Laboratory of Medical Sciences Imperial College London UK.

Journal of the American Heart Association
|December 11, 2025
PubMed
Summary
This summary is machine-generated.

Polygenic risk scores (PRS) offer modest improvement for predicting preeclampsia in European ancestry women. Their utility is limited in African ancestry women due to underrepresentation in genetic studies, highlighting a need for equitable development.

Keywords:
ancestrygenomicspolygenic scorepreeclampsiapregnancyrisk prediction

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Area of Science:

  • Genetics and Genomics
  • Maternal-Fetal Medicine
  • Reproductive Health

Background:

  • Preeclampsia poses significant risks to maternal and fetal well-being.
  • Early identification of high-risk pregnancies is crucial for implementing preventative measures.
  • The predictive value of polygenic risk scores (PRS) for preeclampsia requires further investigation, especially across diverse ancestries.

Purpose of the Study:

  • To evaluate the added predictive value of preeclampsia and systolic blood pressure PRS in first-trimester prediction models.
  • To compare PRS performance against established clinical and advanced prediction models.
  • To assess PRS performance across different ancestral groups.

Main Methods:

  • Two prospective pregnancy cohorts (Fetal Medicine Foundation and Pregnancy Outcome Prediction studies) were analyzed.
  • Risk models incorporated clinical factors, PRS, and advanced first-trimester markers (mean arterial pressure, PAPP-A, uterine artery pulsatility index).
  • Discriminative performance was measured using the area under the receiver operating characteristic curve (AUC) and assessed by ancestry.

Main Results:

  • Preeclampsia PRS showed independent association with preeclampsia, modestly improving prediction over clinical models (AUC 0.746 vs. 0.750).
  • No significant improvement was observed when PRS were added to the advanced model (AUC 0.817 vs. 0.818).
  • Systolic blood pressure PRS improved prediction in European ancestry women but not in African ancestry women.

Conclusions:

  • PRS for preeclampsia and systolic blood pressure offer limited additional predictive value beyond clinical factors in European ancestry women.
  • Underrepresentation in genome-wide association studies limits the utility of current PRS in African ancestry populations.
  • Refined PRS models and larger cohorts may enhance equitable risk stratification in maternal health in the future.