{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:07:11Z","timestamp":1779325631801,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Preeclampsia and gestational hypertensive disorders (GHD) are common complications of pregnancy that adversely affect maternal and offspring health, often with long-term consequences. High BMI, advanced age, and pre-existing conditions are known risk factors for GHD. Yet, assessing a woman\u2019s risk of GHD based on only these characteristics needs to be reevaluated in order to identify at-risk women, facilitate early diagnosis, and implement lifestyle recommendations. This study demonstrates that a risk score developed with machine learning from the case-control genetics dataset can be used as an early screening test for GHD. We further confirm BMI as a risk factor for GHD and investigate a relationship between GHD and genetically constructed anthropometric measures and biomarkers. Our results show that polygenic risk score can be used as an early screening tool that, together with other known risk factors and medical history, would assist in identifying women at higher risk of GHD before its onset to enable stratification of patients into low-risk and high-risk groups for monitoring and preventative programs to mitigate the risks.<\/jats:p>","DOI":"10.3390\/jpm12111826","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:53:07Z","timestamp":1667447587000},"page":"1826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Polygenic Risk Score and Risk Factors for Preeclampsia and Gestational Hypertension"],"prefix":"10.3390","volume":"12","author":[{"given":"Marija Majda","family":"Peri\u0161i\u0107","sequence":"first","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"},{"name":"Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klemo","family":"Vladimir","sequence":"additional","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"},{"name":"Faculty of Electrical Engineering and Computing, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Karpov","sequence":"additional","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"\u0160torga","sequence":"additional","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"},{"name":"Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Mostashari","sequence":"additional","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raya","family":"Khanin\u00a0","sequence":"additional","affiliation":[{"name":"LifeNome Inc., New York, NY 10018, USA"},{"name":"Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s40883-021-00243-w","article-title":"Pre-eclampsia: A Scoping Review of Risk Factors and Suggestions for Future Research Direction","volume":"8","author":"Lee","year":"2022","journal-title":"Regen. Eng. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/NMC.0000000000000523","article-title":"Gestational hypertension and preeclampsia","volume":"44","author":"Wisner","year":"2019","journal-title":"MCN Am. J. Matern. Nurs."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1111\/nure.12055","article-title":"Epidemiology of preeclampsia: Impact of obesity","volume":"71","author":"Jeyabalan","year":"2013","journal-title":"Nutr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E44","DOI":"10.1097\/AOG.0000000000002708","article-title":"Low-dose aspirin use during pregnancy","volume":"132","author":"Porter","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"c3209","DOI":"10.1136\/bmj.c3209","article-title":"Management of bacterial meningitis and meningococcal septicaemia in children and young people: Summary of NICE guidance","volume":"340","author":"Visintin","year":"2010","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/uog.19039","article-title":"Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: Results of SPREE","volume":"51","author":"Tan","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103780","DOI":"10.1016\/j.ebiom.2021.103780","article-title":"Clinical tools and biomarkers to predict preeclampsia","volume":"75","author":"MacDonald","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/ajmg.a.30257","article-title":"Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: A population-based Swedish cohort study","volume":"130","author":"Cnattingius","year":"2004","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101535","DOI":"10.1016\/j.arr.2021.101535","article-title":"Pregnancy, preeclampsia and maternal aging: From epidemiology to functional genomics","volume":"73","author":"Miller","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_10","first-page":"2202","article-title":"Association between gene polymorphisms on chromosome 1 and susceptibility to pre-eclampsia: An updated meta-analysis","volume":"22","author":"Zhang","year":"2016","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s10038-005-0270-8","article-title":"The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia","volume":"50","author":"Hillermann","year":"2005","journal-title":"J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, F., Rouault, C., Cl\u00e9ment, K., Zhu, W., Degrelle, S.A., Charles, M.A., Heude, B., and Fournier, T. (2021). C1431T Variant of PPAR\u03b3 Is Associated with Preeclampsia in Pregnant Women. Life, 11.","DOI":"10.3390\/life11101052"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6764","DOI":"10.1038\/s41598-021-86240-z","article-title":"Genetic association of ERAP1 and ERAP2 with eclampsia and preeclampsia in northeastern Brazilian women","volume":"11","author":"Ferreira","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/hmg\/ddu423","article-title":"Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia","volume":"24","author":"Oudejans","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","first-page":"1033","article-title":"Glutathione S-transferase isoenzymes in decidua and placenta of preeclamptic pregnancies","volume":"94","author":"Zusterzeel","year":"1999","journal-title":"Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s00438-022-01889-z","article-title":"Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population","volume":"297","author":"Xin","year":"2022","journal-title":"Mol. Genet. Genom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00439-006-0281-3","article-title":"Extremely skewed X-chromosome inactivation is increased in pre-eclampsia","volume":"121","author":"Uz","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/MD.0000000000027437","article-title":"Association of IL-10-819C\/T, -592A\/C polymorphisms with the risk of preeclampsia: An updated meta-analysis","volume":"100","author":"Che","year":"2021","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1053\/j.ajkd.2020.10.020","article-title":"Joint associations of maternal-fetal APOL1 genotypes and maternal country of origin with preeclampsia risk","volume":"77","author":"Hong","year":"2021","journal-title":"Am. J. Kidney Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tyrmi, J.S., Kaartokallio, T., Lokki, A.I., J\u00e4\u00e4skel\u00e4inen, T., Kortelainen, E., Ruotsalainen, S.S., Karjalainen, J., Ripatti, S., Laisk, T., and Kettunen, J. (2022). GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function. medRxiv.","DOI":"10.1101\/2022.05.19.22275002"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5976","DOI":"10.1038\/s41467-020-19733-6","article-title":"Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women","volume":"11","author":"Steinthorsdottir","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Perisic, M.M., Vladimir, K., Storga, M., Mostashari, A., and Khanin, R. (2022). Polygenic Risk Score and Risk Factors for Gestational Diabetes. J. Pers. Med., 12.","DOI":"10.20944\/preprints202207.0305.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W185","DOI":"10.1093\/nar\/gkaa420","article-title":"SNPnexus: A web server for functional annotation of human genome sequence variation (2020 update)","volume":"48","author":"Oscanoa","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W109","DOI":"10.1093\/nar\/gky399","article-title":"SNPnexus: Assessing the functional relevance of genetic variation to facilitate the promise of precision medicine","volume":"46","author":"Oscanoa","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","first-page":"463","article-title":"The relationship between body mass index and preeclampsia: A systematic review and meta-analysis","volume":"17","author":"Motedayen","year":"2019","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_27","first-page":"486","article-title":"Maternal obesity and energy intake as risk factors of pregnancy-induced hypertension among Iranian women","volume":"32","author":"Kazemian","year":"2014","journal-title":"J. Health Popul. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1001\/jamacardio.2018.1717","article-title":"Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK Biobank Study","volume":"3","author":"Said","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_29","first-page":"1","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat. Rev. Methods Prim."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1161\/HYPERTENSIONAHA.121.18617","article-title":"Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study","volume":"79","author":"Ardissino","year":"2022","journal-title":"Hypertension"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s42003-021-02550-y","article-title":"Composite trait Mendelian randomization reveals distinct metabolic and lifestyle consequences of differences in body shape","volume":"4","author":"Sulc","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Williams, M.A., Zingheim, R.W., King, I.B., and Zebelman, A.M. (1995). Omega-3 fatty acids in maternal erythrocytes and risk of preeclampsia. Epidemiology, 232\u2013237.","DOI":"10.1097\/00001648-199505000-00007"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/nyas.14093","article-title":"Maternal hemoglobin concentrations across pregnancy and maternal and child health: A systematic review and meta-analysis","volume":"1450","author":"Young","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13293-022-00436-0","article-title":"The diagnostic potential of oxidative stress biomarkers for preeclampsia: Systematic review and meta-analysis","volume":"13","author":"Afrose","year":"2022","journal-title":"Biol. Sex Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S1071","DOI":"10.1016\/j.ajog.2020.07.020","article-title":"First trimester preeclampsia screening and prediction","volume":"226","author":"Chaemsaithong","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.placenta.2020.01.008","article-title":"A review of omics approaches to study preeclampsia","volume":"92","author":"Benny","year":"2020","journal-title":"Placenta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1038\/s41591-021-01549-6","article-title":"Responsible use of polygenic risk scores in the clinic: Potential benefits, risks and gaps","volume":"27","author":"Adeyemo","year":"2021","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/hmg\/ddx375","article-title":"The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle","volume":"27","author":"Ren","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Burchakov, D.I., Kuznetsova, I.V., and Uspenskaya, Y.B. (2017). Omega-3 long-chain polyunsaturated fatty acids and preeclampsia: Trials say \u201cno,\u201d but is it the final word?. Nutrients, 9.","DOI":"10.3390\/nu9121364"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s41232-021-00172-9","article-title":"Statistical genetics and polygenic risk score for precision medicine","volume":"41","author":"Konuma","year":"2021","journal-title":"Inflamm. Regen."},{"key":"ref_42","first-page":"194","article-title":"High maternal hemoglobin concentration in first trimester as risk factor for pregnancy induced hypertension","volume":"2","author":"Aghamohammadi","year":"2011","journal-title":"Casp. J. Intern. Med."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:41Z","timestamp":1760144981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jpm12111826"],"URL":"https:\/\/doi.org\/10.3390\/jpm12111826","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]}}}