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Polygenic Risk Score to Predict Preeclampsia, Gestational Hypertension in Pregnant Women

In a new genome-wide association study (GWAS) published in Nature Medicine, researchers from Massachusetts General Hospital and elsewhere identify 18 genetic loci associated with preeclampsia, eclampsia, or gestational hypertension, 12 of which are novel. These three conditions fall under the umbrella of hypertensive disorders of pregnancy (HDPs), the leading cause of maternal and neonatal deaths. The authors studied maternal DNA variants in 20,064 cases with preeclampsia and 703,117 control individuals, along with 11,027 cases of gestational hypertension and 412,788 controls. The control group included pregnant women with normal blood pressure and no hypertension. The researchers conducted a multi-ancestry meta-analysis that identified loci that highlight the roles of genes involved in natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development, and immune dysregulation, the authors note. The findings not only reveal mechanistic insights into the pathophysiology of HDP but could also lead to the development of therapeutics to prevent or even treat HDPS, according to the authors. For instance, synthetic natriuretic peptides such as nesiritide may represent a future HDP therapeutic target. Meanwhile, the researchers also developed genome-wide polygenic risk scores to predict preeclampsia, eclampsia, and gestational hypertension, which they validated in external cohorts. "Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification," the authors write.