Polygenic risk scores for hypertensive disorders of pregnancy and later-life cardiovascular disease in women
- 1Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia.
Abstract
ObjectivesTo investigate whether genetic predisposition to hypertensive disorders of pregnancy (HDP), measured using polygenic risk scores (PRS), is associated with subsequent cardiovascular disease (CVD) outcomes in analyses stratified by HDP history.
Study design and main outcome measuresThis population-based cohort included 1,284 women from the 1994-95 Busselton Health Study with genotype data, pregnancy history, cardiovascular risk factors, and linked hospitalisation and death records to 2022. Four HDP-related PRS were assessed: two for preeclampsia, one for gestational hypertension, and one for broad HDP phenotype. Outcomes were incident first CVD events classified into categories. Fine-Gray competing-risk models adjusted for age, cardiovascular risk factors, and genetic principal components estimated subdistribution hazard ratios (sHR) per standard deviation increase in PRS.
ResultsOf 1,284 women, 309 reported a history of HDP and 651 experienced an incident CVD event during follow-up. In analyses stratified by HDP history, the largest estimates were observed for first cerebrovascular disease, although event numbers were small. The PGS003586 preeclampsia PRS showed the largest estimate (sHR 3.41, 95% confidence interval (CI) 1.54-7.58, p = 0.003), while PGS004593, another preeclampsia-related score, was also positively associated with cerebrovascular disease (sHR 1.86, 95% CI 1.05-3.30, p = 0.035). The gestational hypertension and broad HDP scores also showed positive estimates, but CI included 1.0, indicating inconclusive evidence.
ConclusionsAmong women with a history of HDP, preeclampsia-related PRS showed preliminary evidence of an association with incident cerebrovascular disease. Given the small number of events, findings should be interpreted cautiously and validated in larger, multi-ancestry cohorts.
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BibTeX
@misc{krishnamurthy2026polygenic,
title = {{Polygenic risk scores for hypertensive disorders of pregnancy and later-life cardiovascular disease in women}},
author = {G. Krishnamurthy and J. A. Temple and M. A. Ahmed and J. Hui and P. J. Meikle and C. Giles and H. T. Phan and S. P. Brennecke and E. K. Moses and P. E. Melton},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.26364560},
url = {https://www.medrxiv.org/content/10.64898/2026.10.01.26364560v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Polygenic risk scores for hypertensive disorders of pregnancy and later-life cardiovascular disease in women
AU - G. Krishnamurthy
AU - J. A. Temple
AU - M. A. Ahmed
AU - J. Hui
AU - P. J. Meikle
AU - C. Giles
AU - H. T. Phan
AU - S. P. Brennecke
AU - E. K. Moses
AU - P. E. Melton
PY - 2026
DA - 2026/10/01
PB - medRxiv
DO - 10.64898/2026.10.01.26364560
UR - https://www.medrxiv.org/content/10.64898/2026.10.01.26364560v1
AB - ObjectivesTo investigate whether genetic predisposition to hypertensive disorders of pregnancy (HDP), measured using polygenic risk scores (PRS), is associated with subsequent cardiovascular disease (CVD) outcomes in analyses stratified by HDP history. Study design and main outcome measuresThis population-based cohort included 1,284 women from the 1994-95 Busselton Health Study with genotype data, pregnancy history, cardiovascular risk factors, and linked hospitalisation and death records to 2022. Four HDP-related PRS were assessed: two for preeclampsia, one for gestational hypertension, and one for broad HDP phenotype. Outcomes were incident first CVD events classified into categories. Fine-Gray competing-risk models adjusted for age, cardiovascular risk factors, and genetic principal components estimated subdistribution hazard ratios (sHR) per standard deviation increase in PRS. ResultsOf 1,284 women, 309 reported a history of HDP and 651 experienced an incident CVD event during follow-up. In analyses stratified by HDP history, the largest estimates were observed for first cerebrovascular disease, although event numbers were small. The PGS003586 preeclampsia PRS showed the largest estimate (sHR 3.41, 95% confidence interval (CI) 1.54-7.58, p = 0.003), while PGS004593, another preeclampsia-related score, was also positively associated with cerebrovascular disease (sHR 1.86, 95% CI 1.05-3.30, p = 0.035). The gestational hypertension and broad HDP scores also showed positive estimates, but CI included 1.0, indicating inconclusive evidence. ConclusionsAmong women with a history of HDP, preeclampsia-related PRS showed preliminary evidence of an association with incident cerebrovascular disease. Given the small number of events, findings should be interpreted cautiously and validated in larger, multi-ancestry cohorts.
ER -