Preeclampsia prediction with maternal and paternal polygenic risk scores: the TMM BirThree Cohort Study

Preeclampsia prediction with maternal and paternal polygenic risk scores: the TMM BirThree Cohort Study

Abstract Genomic information from pregnant women and the paternal parent of their fetuses may provide effective biomarkers for preeclampsia (PE). This study investigated the association of parental polygenic risk scores (PRSs) for blood pressure (BP) and PE with PE onset and evaluated predictive per...

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Main Authors: Hisashi Ohseto, Mami Ishikuro, Taku Obara, Akira Narita, Ippei Takahashi, Genki Shinoda, Aoi Noda, Keiko Murakami, Masatsugu Orui, Noriyuki Iwama, Masahiro Kikuya, Hirohito Metoki, Junichi Sugawara, Gen Tamiya, Shinichi Kuriyama
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
BirThree Cohort Study
Family history
Genome-wide association study
Hypertensive disorders of pregnancy
LDpred2
Online Access:https://doi.org/10.1038/s41598-025-97291-x
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Summary:Abstract Genomic information from pregnant women and the paternal parent of their fetuses may provide effective biomarkers for preeclampsia (PE). This study investigated the association of parental polygenic risk scores (PRSs) for blood pressure (BP) and PE with PE onset and evaluated predictive performances of PRSs using clinical predictive variables. In the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, 19,836 participants were genotyped using either Affymetrix Axiom Japonica Array v2 (further divided into two cohorts—the PRS training cohort and the internal-validation cohort—at a ratio of 1:2) or Japonica Array NEO (external-validation cohort). PRSs were calculated for systolic BP (SBP), diastolic BP (DBP), and PE and hyperparameters for PRS calculation were optimized in the training cohort. PE onset was associated with maternal SBP-, DBP-, and PE-PRSs and paternal SBP- and DBP-PRSs only in the external-validation cohort. Meta-analysis revealed overall associations with maternal PRSs but highlighted significant heterogeneity between cohorts. Maternal DBP-PRS calculated using “LDpred2” presented the most improvement in prediction models and provided additional predictive information on clinical predictive variables. Paternal DBP-PRS improved prediction models in the internal-validation cohort. In conclusion, Parental PRS, along with clinical predictive variables, is potentially useful for predicting PE.
ISSN:2045-2322

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