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

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.