Genetic predictors of blood pressure traits are associated with preeclampsia

Abstract

Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University’s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (ORDBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10−3; ORSBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10−6; ORPP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10−5). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.