{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:23Z","timestamp":1790189963213,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The hypertensive disorders of pregnancy (HDPs), that is, preeclampsia and gestational hypertension, are characterized by endothelial dysfunction in pregnancy and are epidemiologically and genetically associated with risk for coronary artery disease (CAD). A recent study suggested that endothelial cell (EC)-acting CAD risk variants may identify individuals who benefit from more intensive lipid-lowering treatment. The present study evaluated whether the same EC CAD genetic risk score is also associated with HDPs using comprehensive statistical genetic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We examined 35 previously identified EC-acting and 205 non-EC-acting risk variants associated with CAD. First, using the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective, multicenter US pregnancy cohort, we calculated polygenic risk scores (PRS) comprised of either EC-acting or non-EC-acting CAD risk variants in genotyped, unrelated participants across multiple ancestry groups. Scores were adjusted for population genetic structure using 10 principal components, then tested for associations with HDPs using logistic regression models adjusted for age. Second, we tested the genetic association of EC-acting and non-EC-acting CAD variants with preeclampsia and gestational hypertension using 2-sample Mendelian randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 6782 unrelated nuMoM2b participants (mean [SD] age, 27.0 [5.5] years, 1040 [15.3%] with HDPs in the index pregnancy), participants with higher EC-acting PRS had a higher incidence of HDPs. Each SD of higher EC-acting PRS was associated with 1.09-fold increased odds of HDP (95% CI, 1.02\u20131.17;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.008); by contrast, the non-EC-acting PRS was not significantly associated with HDP risk (odds ratio, 1.05 [95% CI, 0.98\u20131.12];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.14). In 2-sample Mendelian randomization, EC-acting CAD variants were strongly associated with both preeclampsia (odds ratio, 1.55 [95% CI, 1.30\u20131.86];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and gestational hypertension (odds ratio, 1.54 [95% CI, 1.29\u20131.85];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>PRS and 2-sample Mendelian randomization approaches suggest enrichment for EC-acting CAD genetic risk variants in women with HDPs. These findings support a shared genetic architecture between HDPs and CAD through endothelial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324519","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:00:38Z","timestamp":1780563638000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Endothelial Susceptibility-Related Genetic Variants and Hypertensive Disorders of Pregnancy\u2014Brief Report"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6350-5121","authenticated-orcid":true,"given":"Linke","family":"Li","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston (L.L., Z.Y., H.T., P.N., M.C.H.)."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2457-2876","authenticated-orcid":true,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Indianapolis (Y.Z., D.M.H., N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0043-0812","authenticated-orcid":true,"given":"Buu","family":"Truong","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston (L.L., Z.Y., H.T., P.N., M.C.H.)."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9865-4106","authenticated-orcid":true,"given":"Rajat M.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."},{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Heart and Vascular Institute, Mass General Brigham, Boston, MA (R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-5398","authenticated-orcid":true,"given":"Haodong","family":"Tian","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston (L.L., Z.Y., H.T., P.N., M.C.H.)."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8402-7435","authenticated-orcid":true,"given":"Pradeep","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston (L.L., Z.Y., H.T., P.N., M.C.H.)."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."},{"name":"Cardiology Division, Massachusetts General Hospital, Heart and Vascular Institute, Mass General Brigham, Boston (P.N., M.C.H.)."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA (P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8379-0743","authenticated-orcid":true,"given":"David M.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Indianapolis (Y.Z., D.M.H., N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Indianapolis (Y.Z., D.M.H., N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5021","authenticated-orcid":true,"given":"Michael C.","family":"Honigberg","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital, Boston (L.L., Z.Y., H.T., P.N., M.C.H.)."},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.L., B.T., Z.Y., R.M.G., H.T., P.N., M.C.H.)."},{"name":"Cardiology Division, Massachusetts General Hospital, Heart and Vascular Institute, Mass General Brigham, Boston (P.N., M.C.H.)."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA (P.N., M.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02374-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.070509"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03533-w"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.01.019"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61218-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq559"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt144"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3679"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu704"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01233-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01714-w"},{"key":"e_1_3_3_17_2","unstructured":"Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Number 222. Obstet Gynecol. 2020. https:\/\/journals.lww.com\/greenjournal\/fulltext\/2020\/06000\/gestational_hypertension_and_preeclampsia__acog.46.aspx"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.02.015"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.324606"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n2233"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.126.324519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:01:00Z","timestamp":1790186460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.126.324519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1161\/ATVBAHA.126.324519"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.126.324519","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}