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Polygenic prediction of preeclampsia and gestational hypertension.
Honigberg, Michael C; Truong, Buu; Khan, Raiyan R; Xiao, Brenda; Bhatta, Laxmi; Vy, Ha My T; Guerrero, Rafael F; Schuermans, Art; Selvaraj, Margaret Sunitha; Patel, Aniruddh P; Koyama, Satoshi; Cho, So Mi Jemma; Vellarikkal, Shamsudheen Karuthedath; Trinder, Mark; Urbut, Sarah M; Gray, Kathryn J; Brumpton, Ben M; Patil, Snehal; Zöllner, Sebastian; Antopia, Mariah C; Saxena, Richa; Nadkarni, Girish N; Do, Ron; Yan, Qi; Pe'er, Itsik; Verma, Shefali Setia; Gupta, Rajat M; Haas, David M; Martin, Hilary C; van Heel, David A; Laisk, Triin; Natarajan, Pradeep.
Afiliação
  • Honigberg MC; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. mhonigberg@mgh.harvard.edu.
  • Truong B; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. mhonigberg@mgh.harvard.edu.
  • Khan RR; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. mhonigberg@mgh.harvard.edu.
  • Xiao B; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Bhatta L; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Vy HMT; Department of Computer Science, Columbia University, New York, NY, USA.
  • Guerrero RF; University of Pennsylvania, Philadelphia, PA, USA.
  • Schuermans A; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Selvaraj MS; HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
  • Patel AP; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Koyama S; Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
  • Cho SMJ; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Vellarikkal SK; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Trinder M; Faculty of Medicine, KU Leuven, Leuven, Belgium.
  • Urbut SM; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Gray KJ; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Brumpton BM; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Patil S; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Zöllner S; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Antopia MC; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Saxena R; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Nadkarni GN; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Do R; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Yan Q; Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, Republic of Korea.
  • Pe'er I; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Verma SS; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Gupta RM; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Haas DM; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
  • Martin HC; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • van Heel DA; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Laisk T; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Natarajan P; Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA.
Nat Med ; 29(6): 1540-1549, 2023 Jun.
Article em En | MEDLINE | ID: mdl-37248299
Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Hipertensão Induzida pela Gravidez / Eclampsia / Hipertensão Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pré-Eclâmpsia / Hipertensão Induzida pela Gravidez / Eclampsia / Hipertensão Idioma: En Ano de publicação: 2023 Tipo de documento: Article