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Genetic Contribution to Preeclampsia and Hypertensive Disorders
Quick Takes
- Cardiovascular disease-related genes are associated with preeclampsia.
- Several genes associated with preeclampsia also have effects on cardiometabolic, endothelial, and placental function.
Study Questions:
What is the genetic contribution to preeclampsia and other hypertensive disorders of pregnancy?
Methods:
This genome-wide association study (GWAS) included data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium. Using International Classification of Diseases codes, individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected and data from 2020-2023 were analyzed. Two phenotypes were analyzed: preeclampsia and preeclampsia or other maternal hypertension during pregnancy.
Results:
Individuals with prior preeclampsia (n = 16,743) and preeclampsia or other maternal hypertension (n = 15,200) were analyzed and genome-wide significant associations were identified. Thirteen of these were novel, and 7 of these were previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). Novel risk loci were also identified in the proximity of genes associated with the development of placenta, remodeling of uterine spiral arteries, kidney function, and maintenance of proteostasis in pregnancy serum.
Conclusions:
Genes related to blood pressure may be abnormal in women with preeclampsia. These genes also have pleiotropic effects on cardiometabolic, endothelial, and placental function. Several associated loci that are abnormal in preeclampsia are associated with maintenance of successful pregnancy.
Perspective:
Pregnancy has been described as a window to future cardiovascular health. In particular, preeclampsia and gestational hypertension are associated with increased long-term cardiovascular risks. Although this association has been well-described, the reasons for the overlap have been unclear, with two main hypotheses: Do individuals with underlying vascular/endothelial dysfunction develop preeclampsia? Or does preeclampsia cause a toxic vascular insult that predisposes to future long-term risk? This GWAS found several genetic loci associated with both preeclampsia and other cardiovascular diseases such as blood pressure. Therefore, this study suggests that genetic susceptibility to cardiovascular disease gets unmasked during pregnancy in the form of preeclampsia. Future studies are needed to learn more about the nuances of these genetic associations.
Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Vascular Medicine, Hypertension
Keywords: Blood Pressure, Cardiometabolic Risk Factors, Endothelium, Vascular, Genome-Wide Association Study, Hypertension, Hypertension, Pregnancy-Induced, Kidney, Metabolic Syndrome, Phenotype, Placenta, Pre-Eclampsia, Pregnancy, Primary Prevention, Proteostasis, Risk Factors, Vascular Diseases, Women
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