{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:08:42Z","timestamp":1790633322835,"version":"4.1.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. However, the current understanding of its underlying biological pathways remains limited.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>In this study, we performed a cross-platform proteome- and transcriptome-wide genetic analysis aimed at evaluating the causal relevance of &gt;2000 circulating proteins with preeclampsia, supported by data on the expression of over 15\u2005000 genes across 36 tissues leveraging large-scale preeclampsia genetic association data from women of European ancestry.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>We demonstrate genetic associations of 18 circulating proteins with preeclampsia (SULT1A1 [sulfotransferase 1A1], SH2B3 [SH2B adapter protein 3], SERPINE2 [serpin family E member 2], RGS18 [regulator of G-protein signaling 18], PZP [pregnancy zone protein], NOTUM [notum, palmitoleoyl-protein carboxylesterase], METAP1 [methionyl aminopeptidase 1], MANEA [mannosidase endo-alpha], jun-D [JunD proto-oncogene], GDF15 [growth differentiation factor 15], FGL1 [fibrinogen like 1], FGF5 [fibroblast growth factor 5], FES [FES proto-oncogene], APOBR [apolipoprotein B receptor], ANP [natriuretic peptide A], ALDH-E2 [aldehyde dehydrogenase 2 family member], ADAMTS13 [ADAM metallopeptidase with thrombospondin type 1 motif 13], and 3MG [N-methylpurine DNA glycosylase]), among which 11 were either directly or indirectly supported by gene expression data, 9 were supported by Bayesian colocalization analyses, and 5 (SERPINE2, PZP, FGF5, FES, and ANP) were supported by all lines of evidence examined. Protein interaction mapping identified potential shared biological pathways through natriuretic peptide signaling, blood pressure regulation, immune tolerance, and thrombin activity regulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>This investigation identified multiple targetable proteins linked to cardiovascular, inflammatory, and coagulation pathways, with SERPINE2, PZP, FGF5, FES, and ANP identified as pivotal proteins with likely causal roles in the development of preeclampsia. The identification of these potential targets may guide the development of targeted therapies for preeclampsia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.124.004755","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T09:12:21Z","timestamp":1723194741000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Proteome- and Transcriptome-Wide Genetic Analysis Identifies Biological Pathways and Candidate Drug Targets for Preeclampsia"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-8117","authenticated-orcid":true,"given":"Maddalena","family":"Ardissino","sequence":"first","affiliation":[{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (M.A., L.G., A.B.), University of Cambridge, United Kingdom."},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute (M.A, 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Unit (E.A.W.S., S.B.), University of Cambridge, United Kingdom."},{"name":"Department of Applied Economics, Erasmus School of Economics (E.A.W.S.), Erasmus University Rotterdam, the Netherlands."},{"name":"Erasmus University Rotterdam Institute for Behavior and Biology (E.A.W.S.), Erasmus University Rotterdam, the Netherlands."},{"name":"Department of Psychology, Education and Child Studies (E.A.W.S.), Erasmus University Rotterdam, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Art","family":"Schuermans","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics and Cardiovascular Disease Initiative (B.T., A.S., P.N., M.C.H.)."},{"name":"Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston (B.T., A.S., P.N., M.C.H.)."},{"name":"Faculty of Medicine, KU Leuven, Belgium 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