Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Valgerdur Steinthorsdottir (), Ralph McGinnis (), Nicholas O. Williams, Lilja Stefansdottir, Gudmar Thorleifsson, Scott Shooter, João Fadista, Jon K. Sigurdsson, Kirsi M. Auro, Galina Berezina, Maria-Carolina Borges, Suzannah Bumpstead, Jonas Bybjerg-Grauholm, Irina Colgiu, Vivien A. Dolby, Frank Dudbridge, Stephanie M. Engel, Christopher S. Franklin, Michael L. Frigge, Yr Frisbaek, Reynir T. Geirsson, Frank Geller, Solveig Gretarsdottir, Daniel F. Gudbjartsson, Quaker Harmon, David Michael Hougaard, Tatyana Hegay, Anna Helgadottir, Sigrun Hjartardottir, Tiina Jääskeläinen, Hrefna Johannsdottir, Ingileif Jonsdottir, Thorhildur Juliusdottir, Noor Kalsheker, Abdumadjit Kasimov, John P. Kemp, Katja Kivinen, Kari Klungsøyr, Wai K. Lee, Mads Melbye, Zosia Miedzybrodska, Ashley Moffett, Dilbar Najmutdinova, Firuza Nishanova, Thorunn Olafsdottir, Markus Perola, Fiona Broughton Pipkin, Lucilla Poston, Gordon Prescott, Saedis Saevarsdottir, Damilya Salimbayeva, Paula Juliet Scaife, Line Skotte, Eleonora Staines-Urias, Olafur A. Stefansson, Karina Meden Sørensen, Liv Cecilie Vestrheim Thomsen, Vinicius Tragante, Lill Trogstad, Nigel A. B. Simpson, Tamara Aripova, Juan P. Casas, Anna F. Dominiczak, James J. Walker, Unnur Thorsteinsdottir, Ann-Charlotte Iversen, Bjarke Feenstra, Deborah A. Lawlor, Heather Allison Boyd, Per Magnus, Hannele Laivuori, Nodira Zakhidova, Gulnara Svyatova, Kari Stefansson and Linda Morgan
Additional contact information
Valgerdur Steinthorsdottir: deCODE genetics/Amgen Inc.
Ralph McGinnis: Wellcome Sanger Institute
Nicholas O. Williams: Wellcome Sanger Institute
Lilja Stefansdottir: deCODE genetics/Amgen Inc.
Gudmar Thorleifsson: deCODE genetics/Amgen Inc.
Scott Shooter: Wellcome Sanger Institute
João Fadista: Statens Serum Institut
Jon K. Sigurdsson: deCODE genetics/Amgen Inc.
Kirsi M. Auro: Finnish Institute for Health and Welfare
Galina Berezina: Scientific Center of Obstetrics, Gynecology and Perinatology
Maria-Carolina Borges: MRC Integrative Epidemiology Unit, University of Bristol
Suzannah Bumpstead: Wellcome Sanger Institute
Jonas Bybjerg-Grauholm: Department for Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut
Irina Colgiu: Wellcome Sanger Institute
Vivien A. Dolby: Leeds Institute of Medical Research (LIMR), School of Medicine, University of Leeds
Frank Dudbridge: London School of Hygiene and Tropical Medicine
Stephanie M. Engel: Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Christopher S. Franklin: Wellcome Sanger Institute
Michael L. Frigge: deCODE genetics/Amgen Inc.
Yr Frisbaek: Landspitali University Hospital
Reynir T. Geirsson: Landspitali University Hospital
Frank Geller: Statens Serum Institut
Solveig Gretarsdottir: deCODE genetics/Amgen Inc.
Daniel F. Gudbjartsson: deCODE genetics/Amgen Inc.
Quaker Harmon: Epidemiology Branch, National Institute of Environmental Health Sciences
David Michael Hougaard: Department for Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut
Tatyana Hegay: Uzbek Academy of Sciences
Anna Helgadottir: deCODE genetics/Amgen Inc.
Sigrun Hjartardottir: Landspitali University Hospital
Tiina Jääskeläinen: Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital
Hrefna Johannsdottir: deCODE genetics/Amgen Inc.
Ingileif Jonsdottir: deCODE genetics/Amgen Inc.
Thorhildur Juliusdottir: deCODE genetics/Amgen Inc.
Noor Kalsheker: University of Nottingham
Abdumadjit Kasimov: Uzbek Academy of Sciences
John P. Kemp: MRC Integrative Epidemiology Unit, University of Bristol
Katja Kivinen: University of Cambridge
Kari Klungsøyr: Division of Mental and Physical Health, Norwegian Institute of Public Health
Wai K. Lee: BHF Glasgow Cardiovascular Research Centre, University of Glasgow
Mads Melbye: Statens Serum Institut
Zosia Miedzybrodska: Division of Applied Medicine, School of Medicine, Medical Sciences, Nutrition and Dentistry, University of Aberdeen
Ashley Moffett: University of Cambridge
Dilbar Najmutdinova: Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology
Firuza Nishanova: Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology
Thorunn Olafsdottir: deCODE genetics/Amgen Inc.
Markus Perola: Finnish Institute for Health and Welfare
Fiona Broughton Pipkin: University of Nottingham
Lucilla Poston: King’s College London
Gordon Prescott: Division of Applied Medicine, School of Medicine, Medical Sciences, Nutrition and Dentistry, University of Aberdeen
Saedis Saevarsdottir: deCODE genetics/Amgen Inc.
Damilya Salimbayeva: Scientific Center of Obstetrics, Gynecology and Perinatology
Paula Juliet Scaife: University of Nottingham
Line Skotte: Statens Serum Institut
Eleonora Staines-Urias: London School of Hygiene and Tropical Medicine
Olafur A. Stefansson: deCODE genetics/Amgen Inc.
Karina Meden Sørensen: The Danish National Biobank, Statens Serum Institut
Liv Cecilie Vestrheim Thomsen: University of Bergen
Vinicius Tragante: deCODE genetics/Amgen Inc.
Lill Trogstad: Norwegian Institute of Public Health
Nigel A. B. Simpson: Division of Womens and Children’s Health, School of Medicine, University of Leeds
Tamara Aripova: Uzbek Academy of Sciences
Juan P. Casas: Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System
Anna F. Dominiczak: BHF Glasgow Cardiovascular Research Centre, University of Glasgow
James J. Walker: Leeds Institute of Medical Research (LIMR), School of Medicine, University of Leeds
Unnur Thorsteinsdottir: deCODE genetics/Amgen Inc.
Ann-Charlotte Iversen: Norwegian University of Science and Technology (NTNU)
Bjarke Feenstra: Statens Serum Institut
Deborah A. Lawlor: MRC Integrative Epidemiology Unit, University of Bristol
Heather Allison Boyd: Statens Serum Institut
Per Magnus: Centre for Fertility and Health, Norwegian Institute of Public Health
Hannele Laivuori: Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital
Nodira Zakhidova: Uzbek Academy of Sciences
Gulnara Svyatova: Scientific Center of Obstetrics, Gynecology and Perinatology
Kari Stefansson: deCODE genetics/Amgen Inc.
Linda Morgan: University of Nottingham

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

Date: 2020
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DOI: 10.1038/s41467-020-19733-6

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