{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:13:49Z","timestamp":1793168029283,"version":"4.5.0"},"reference-count":59,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:sec id=\"ab-hoi230025-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230025-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230025-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>\n                      This GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. 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 GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant\n                      <jats:italic>International Classification of Diseases<\/jats:italic>\n                      codes. Data were analyzed from July 2020 to February 2023.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230025-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>The association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230025-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 16\u202f743 women with prior preeclampsia and 15\u202f200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (\n                      <jats:italic>NPPA<\/jats:italic>\n                      ,\n                      <jats:italic>NPR3<\/jats:italic>\n                      ,\n                      <jats:italic>PLCE1<\/jats:italic>\n                      ,\n                      <jats:italic>TNS2<\/jats:italic>\n                      ,\n                      <jats:italic>FURIN<\/jats:italic>\n                      ,\n                      <jats:italic>RGL3<\/jats:italic>\n                      , and\n                      <jats:italic>PREX1<\/jats:italic>\n                      ). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (\n                      <jats:italic>PGR<\/jats:italic>\n                      ,\n                      <jats:italic>TRPC6<\/jats:italic>\n                      ,\n                      <jats:italic>ACTN4<\/jats:italic>\n                      , and\n                      <jats:italic>PZP<\/jats:italic>\n                      ), remodeling of uterine spiral arteries (\n                      <jats:italic>NPPA<\/jats:italic>\n                      ,\n                      <jats:italic>NPPB<\/jats:italic>\n                      ,\n                      <jats:italic>NPR3<\/jats:italic>\n                      , and\n                      <jats:italic>ACTN4<\/jats:italic>\n                      ), kidney function (\n                      <jats:italic>PLCE1<\/jats:italic>\n                      ,\n                      <jats:italic>TNS2<\/jats:italic>\n                      ,\n                      <jats:italic>ACTN4<\/jats:italic>\n                      , and\n                      <jats:italic>TRPC6<\/jats:italic>\n                      ), and maintenance of proteostasis in pregnancy serum (\n                      <jats:italic>PZP<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230025-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2023.1312","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T11:04:35Z","timestamp":1686135875000},"page":"674","source":"Crossref","is-referenced-by-count":155,"title":["Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy"],"prefix":"10.1001","volume":"8","author":[{"given":"Jaakko S.","family":"Tyrmi","sequence":"first","affiliation":[{"name":"Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland"},{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea","family":"Kaartokallio","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Inkeri","family":"Lokki","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"J\u00e4\u00e4skel\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Department of Food and Nutrition, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija","family":"Kortelainen","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanni","family":"Ruotsalainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Karjalainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"},{"name":"Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston"},{"name":"Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuli","family":"Ripatti","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"},{"name":"Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge"},{"name":"Department of Public Health, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kivioja","sequence":"additional","affiliation":[{"name":"Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triin","family":"Laisk","sequence":"additional","affiliation":[{"name":"Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kettunen","sequence":"additional","affiliation":[{"name":"Biocenter Oulu, University of Oulu, Oulu, Finland"},{"name":"Finnish Institute for Health and Welfare, Helsinki, 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Hospital, Helsinki, Finland"},{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Health and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Heinonen","sequence":"additional","affiliation":[{"name":"Department of Obsterics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Kere","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden"},{"name":"Folkh\u00e4lsan Research Center and Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannele","family":"Laivuori","sequence":"additional","affiliation":[{"name":"Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, 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