{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:50:04Z","timestamp":1791370204649,"version":"4.3.1"},"posted":{"date-parts":[[2026,10,2]]},"group-title":"Genetic and Genomic Medicine","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council","award":["APP2001203"],"award-info":[{"award-number":["APP2001203"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Health and Medical Research Council","award":["APP2028555"],"award-info":[{"award-number":["APP2028555"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tasmania Graduate Research Scholarship (TGRS) from the University of Tasmania","id":[{"id":"https:\/\/ror.org\/01nfmeh72","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Menzies Institute for Medical Research Top-up Scholarship","id":[{"id":"https:\/\/ror.org\/04yvxvx65","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study design and main outcome measures<\/jats:title>\n                  <jats:p>This 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.10.01.26364560","type":"posted-content","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:20:14Z","timestamp":1790986814000},"source":"Crossref","is-referenced-by-count":0,"title":["Polygenic risk scores for hypertensive disorders of pregnancy and later-life cardiovascular disease in women"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-9398","authenticated-orcid":false,"given":"Gayathry","family":"Krishnamurthy","sequence":"first","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2879-1329","authenticated-orcid":false,"given":"James A.","family":"Temple","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-2496","authenticated-orcid":false,"given":"Jennie","family":"Hui","sequence":"additional","affiliation":[{"name":"Busselton Population Medical Research Institute, Busselton, WA, 6280, Australia"},{"name":"School of Population and Global Health, The University of Western Australia, Crawley, WA, 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-4665","authenticated-orcid":false,"given":"Peter J.","family":"Meikle","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia"},{"name":"Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, 3010, Australia"},{"name":"Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, VIC, 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6050-1259","authenticated-orcid":false,"given":"Corey","family":"Giles","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia"},{"name":"Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, 3010, Australia"},{"name":"Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, VIC, 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0506-2924","authenticated-orcid":false,"given":"Hoang T.","family":"Phan","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"},{"name":"Menzies School of Health Research, Centre for Child Development, The Charles Darwin University, Darwin, NT, 0810, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-6971","authenticated-orcid":false,"given":"Shaun P.","family":"Brennecke","sequence":"additional","affiliation":[{"name":"Pregnancy Research Centre, Department of Maternal-Fetal Medicine, The Royal Women\u2019s Hospital, Melbourne, VIC, 3050, Australia"},{"name":"Department of Obstetrics, Gynaecology and Newborn Health, The Royal Women\u2019s Hospital, The University of Melbourne, Melbourne, VIC, 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7781-4465","authenticated-orcid":false,"given":"Eric K.","family":"Moses","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-2964","authenticated-orcid":false,"given":"Phillip E.","family":"Melton","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, The University of Tasmania, Hobart, TAS, 7000, Australia"},{"name":"School of Population and Global Health, The University of Western Australia, Crawley, WA, 6009, Australia"},{"name":"Curtin School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, WA, 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100702550839000_2026.10.01.26364560v1.1","unstructured":"World Heart Federation, Women & CVD. https:\/\/world-heart-federation.org\/heart-health\/women-cvd\/ (accessed 29 July 2026)."},{"key":"2026100702550839000_2026.10.01.26364560v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxt006"},{"key":"2026100702550839000_2026.10.01.26364560v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccl.2020.09.005"},{"key":"2026100702550839000_2026.10.01.26364560v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2021.09.008"},{"key":"2026100702550839000_2026.10.01.26364560v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.03.034"},{"key":"2026100702550839000_2026.10.01.26364560v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.15394"},{"key":"2026100702550839000_2026.10.01.26364560v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/uog.22107"},{"key":"2026100702550839000_2026.10.01.26364560v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.116.003497"},{"key":"2026100702550839000_2026.10.01.26364560v1.9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276"},{"key":"2026100702550839000_2026.10.01.26364560v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"},{"key":"2026100702550839000_2026.10.01.26364560v1.11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317189"},{"key":"2026100702550839000_2026.10.01.26364560v1.12","doi-asserted-by":"publisher","DOI":"10.3389\/fepid.2023.1221222"},{"key":"2026100702550839000_2026.10.01.26364560v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gat011"},{"key":"2026100702550839000_2026.10.01.26364560v1.14","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2023.1312"},{"key":"2026100702550839000_2026.10.01.26364560v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02374-9"},{"key":"2026100702550839000_2026.10.01.26364560v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3895"},{"key":"2026100702550839000_2026.10.01.26364560v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19733-6"},{"key":"2026100702550839000_2026.10.01.26364560v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0353-1"},{"key":"2026100702550839000_2026.10.01.26364560v1.19","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001077"},{"key":"2026100702550839000_2026.10.01.26364560v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0800-0"},{"key":"2026100702550839000_2026.10.01.26364560v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.07.079"},{"key":"2026100702550839000_2026.10.01.26364560v1.22","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003336"},{"key":"2026100702550839000_2026.10.01.26364560v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.03.013"},{"key":"2026100702550839000_2026.10.01.26364560v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56107-2"},{"key":"2026100702550839000_2026.10.01.26364560v1.25","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.70021"},{"key":"2026100702550839000_2026.10.01.26364560v1.26","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1999.10474144"},{"key":"2026100702550839000_2026.10.01.26364560v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7501"},{"key":"2026100702550839000_2026.10.01.26364560v1.28","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017719"},{"key":"2026100702550839000_2026.10.01.26364560v1.29","unstructured":"Busselton Population Medical Research Institute (BPMRI), Busselton Health Study. https:\/\/bpmri.org.au\/ (accessed 29 July 2026)."},{"key":"2026100702550839000_2026.10.01.26364560v1.30","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1856-x"},{"key":"2026100702550839000_2026.10.01.26364560v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30875-7"},{"key":"2026100702550839000_2026.10.01.26364560v1.32","doi-asserted-by":"publisher","DOI":"10.1097\/HJR.0b013e32832955fc"},{"key":"2026100702550839000_2026.10.01.26364560v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30664-0"},{"key":"2026100702550839000_2026.10.01.26364560v1.34","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"2026100702550839000_2026.10.01.26364560v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"2026100702550839000_2026.10.01.26364560v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj144"},{"key":"2026100702550839000_2026.10.01.26364560v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"2026100702550839000_2026.10.01.26364560v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3679"},{"key":"2026100702550839000_2026.10.01.26364560v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"2026100702550839000_2026.10.01.26364560v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00783-5"},{"key":"2026100702550839000_2026.10.01.26364560v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01937-x"},{"key":"2026100702550839000_2026.10.01.26364560v1.42","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.14211027"},{"key":"2026100702550839000_2026.10.01.26364560v1.43","unstructured":"R Core Team, R: A language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria, 2025. https:\/\/www.R-project.org\/."},{"key":"2026100702550839000_2026.10.01.26364560v1.44","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11513"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.10.01.26364560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:55:15Z","timestamp":1791366915000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.10.01.26364560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":44,"URL":"https:\/\/doi.org\/10.64898\/2026.10.01.26364560","relation":{},"subject":[],"published":{"date-parts":[[2026,10,2]]},"subtype":"preprint"}}