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

Area of Science:

• Genomics
• Obstetrics
• Cardiovascular Science

Background:

• Preeclampsia (PE) poses significant risks during pregnancy.
• Identifying effective biomarkers for PE prediction is crucial for maternal health.
• Genomic data from parents may offer novel predictive insights.

Purpose of the Study:

• To investigate the association between parental polygenic risk scores (PRS) for blood pressure (BP) and PE with PE onset.
• To evaluate the predictive performance of PRS when integrated with clinical variables.

Main Methods:

• Utilized data from 19,836 participants in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.
• Genotyped participants and calculated PRS for systolic BP, diastolic BP, and PE.
• Optimized PRS calculation and evaluated predictive models in training, internal-validation, and external-validation cohorts.

Main Results:

• Parental PRS for SBP, DBP, and PE were associated with PE onset in the external-validation cohort.
• Maternal PRS showed overall associations, but with significant heterogeneity between cohorts.
• Maternal diastolic BP-PRS, calculated using LDpred2, significantly improved prediction models.
• Paternal diastolic BP-PRS also enhanced prediction models in the internal-validation cohort.

Conclusions:

• Parental PRS hold potential as predictive biomarkers for preeclampsia.
• Integrating parental PRS with existing clinical variables can improve PE prediction accuracy.
• Further research is warranted to refine the utility of PRS in clinical PE risk assessment.