University of Oulu

Steinthorsdottir, V., McGinnis, R., Williams, N.O. et al. Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nat Commun 11, 5976 (2020). https://doi.org/10.1038/s41467-020-19733-6

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

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Author: Steinthorsdottir, Valgerdur1; McGinnis, Ralph2; Williams, Nicholas O.2;
Stefansdottir, Lilja; Thorleifsson, Gudmar1; Shooter, Scott; Fadista, Joao3,4; Sigurdsson, Jon K.1; Auro, Kirsi M.5; Berezina, Galina6; Borges, Maria-Carolina7,8; Bumpstead, Suzannah; Bybjerg-Grauholm, Jonas9; Colgiu, Irina; Dolby, Vivien A.10; Dudbridge, Frank; Engel, Stephanie M.11; Franklin, Christopher S.; Frigge, Michael L.1; Frisbaek, Yr12; Geirsson, Reynir T.13,12; Geller, Frank; Gretarsdottir, Solveig1; Gudbjartsson, Daniel F.14; Harmon, Quaker15; Hougaard, David Michael; Hegay, Tatyana16; Helgadottir, Anna1; Hjartardottir, Sigrun; Jaeaeskelaeinen, Tiina17,18; Johannsdottir, Hrefna; Jonsdottir, Ingileif19; Juliusdottir, Thorhildur1; Kalsheker, Noor19,20; Kasimov, Abdumadjit; Kemp, John P.21; Kivinen, Katja22; Klungsoyr, Kari23,24; Lee, Wai K.25; Melbye, Mads26,27; Miedzybrodska, Zosia28; Moffett, Ashley29; Najmutdinova, Dilbar30; Nishanova, Firuza30; Olafsdottir, Thorunn; Perola, Markus31; Pipkin, Fiona Broughton32; Poston, Lucilla33; Prescott, Gordon34; Saevarsdottir, Saedis1; Salimbayeva, Damilya; Scaife, Paula Juliet; Skotte, Line3; Staines-Urias, Eleonora; Stefansson, Olafur A.1; Sorensen, Karina Meden35; Thomsen, Liv Cecilie Vestrheim36,37; Tragante, Vinicius1,38; Trogstad, Lill39; Simpson, Nigel A. B.40; Laivuori, Hannele41,42,43; Morgan, Linda19; Aripova, Tamara16; Casas, Juan P.44,45; Dominiczak, Anna F.24; Walker, James J.10; Thorsteinsdottir, Unnur; Iversen, Ann-Charlotte; Feenstra, Bjarke3; Lawlor, Deborah A.7,8,46; Boyd, Heather Allison3; Magnus, Per47; Laivuori, Hannele41,42,43; Zakhidova, Nodira; Svyatova, Gulnara6; Stefansson, Kari; Morgan, Linda19; Laivuori, Hannele41,42,43; Heinonen, Seppo48,18; Kajantie, Eero18,49,50,51,52,53; Kere, Juha54,55,56,57; Kivinen, Katja22; Pouta, Anneli58; Morgan, Linda19; Pipkin, Fiona Broughton32; Kalsheker, Noor19,20; Walker, James J.10; Macphail, Sheila59; Kilby, Mark60; Habiba, Marwan61; Williamson, Catherine62; O'Shaughnessy, Kevin63; O'Brien, Shaughn64; Cameron, Alan24; Redman, Christopher W. G.65; Farrall, Martin66; Caulfield, Mark67; Dominiczak, Anna F.24
Organizations: 1Amgen Inc, IdeCODE Genet, Reykjavik, Iceland.
2Wellcome Sanger Inst, Cambridge, England.
3Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.
4Lund Univ, Dept Clin Sci, Diabet Ctr, Malmo, Sweden.
5Finnish Inst Hlth & Welf, Helsinki, Finland.
6Sci Ctr Obstet Gynecol & Perinatol, Alma Ata, Kazakhstan.
7Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
8Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
9Statens Serum Inst, Dept Congenital Disorders, Danish Ctr Neonatal Screening, Copenhagen, Denmark.
10Univ Leeds, Leeds Inst Med Res LIMR, Sch Med, Leeds, W Yorkshire, England.
11Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
12Landspitali Univ Hosp, Dept Obstet & Gynecol, Reykjavik, Iceland.
13London Sch Hyg & Trop Med, Dept Non Communicable Dis Epidemiol, London, England.
14Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland.
15Natl Inst Environm Hlth Sci, Epidemiol Branch, Durham, NC USA.
16Uzbek Acad Sci, Inst Immunol & Human Genom, Tashkent, Uzbekistan.
17Univ Helsinki, Med & Clin Genet, Helsinki, Finland.
18Helsinki Univ Hosp, Helsinki, Finland.
19Univ Iceland, Fac Med, Reykjavik, Iceland.
20Univ Nottingham, Sch Life Sci, Nottingham, England.
21Univ Queensland, Diamantina Inst, Woolloongabba, Qld, Australia.
22Univ Cambridge, Div Cardiovasc Med, Cambridge, England.
23Norwegian Inst Publ Hlth, Div Mental & Phys Hlth, Oslo, Norway.
24Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
25Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
26Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark.
27Stanford Univ, Sch Med, Dept Med, Stanford, CA USA.
28Univ Aberdeen, Sch Med Med Sci Nutr & Dent, Div Appl Med, Aberdeen, Scotland.
29Univ Cambridge, Dept Pathol, Cambridge, England.
30Republ Specialized Sci Pract Med Ctr Obstet & Gyn, Tashkent, Uzbekistan.
31Univ Helsinki, Res Program Clin & Mol Metab, Fac Med, Helsinki, Finland.
32Univ Nottingham, Sch Med, Nottingham, England.
33Kings Coll London, Dept Women & Childrens Hlth, London, England.
34Univ Cent Lancashire, Lancashire Clin Trials Unit, Preston, Lancs, England.
35Statens Serum Inst, Danish Natl Biobank, Copenhagen, Denmark.
36Univ Bergen, Ctr Canc Biomarkers CCBIO, Dept Clin Sci, Bergen, Norway.
37Norwegian Univ Sci & Technol NTNU, Dept Clin & Mol Med, CEMIR, Trondheim, Norway.
38Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
39Norwegian Inst Publ Hlth, Dept Infect Dis Epidemiol & Modelling, Oslo, Norway.
40Univ Leeds, Sch Med, Div Womens & Childrens Hlth, Leeds, W Yorkshire, England.
41Univ Helsinki, Helsinki Inst Life Sci, Helsinki, Finland.
42Tampere Univ Hosp, Dept Obstet & Gynecol, 1, Tampere, Finland.
43Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland.
44VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
45Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
46Bristol NIHR Biomed Res Ctr, Bristol, Avon, England.
47Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway.
48Univ Helsinki, Obstet & Gynecol, Helsinki, Finland.
49Oulu Univ Hosp, PEDEGO Res Unit, Med Res Ctr Oulu, Oulu, Finland.
50Univ Oulu, Oulu, Finland.
51Natl Inst Hlth & Welf, Publ Hlth Promot Unit, Helsinki, Finland.
52Univ Helsinki, Childrens Hosp, Helsinki, Finland.
53Norwegian Univ Hlth & Technol, Dept Clin & Mol Med, Trondheim, Norway.
54Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
55Univ Helsinki, Folkhalsan Inst Genet, Helsinki, Finland.
56Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.
57Kings Coll London, Sch Basic Med Biosci, London, England.
58Natl Inst Hlth & Welf, Dept Govt Serv, Helsinki, Finland.
59Newcastle Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England.
60Univ Birmingham, Coll Med & Dent Sci, Ctr Womens Newborn Hlth, Birmingham, W Midlands, England.
61Univ Leicester, Leicester, Leics, England.
62Kings Coll London, Div Womens Hlth, London, England.
63Univ Cambridge, Dept Med, Cambridge, England.
64Keele Univ, Sch Med, Stoke On Trent, Staffs, England.
65Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England.
66Univ Oxford, Dept Med, Oxford, England.
67Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London, England.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021082343899
Language: English
Published: Springer Nature, 2020
Publish Date: 2021-08-23
Description:

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. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 11
Issue: 1
Article number: 5976
DOI: 10.1038/s41467-020-19733-6
OADOI: https://oadoi.org/10.1038/s41467-020-19733-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: Research leading to these results was conducted as part of the InterPregGen study, which received funding from the European Union Seventh Framework Programme under grant agreement no. 282540 and was supported by Wellcome Trust grant 098051. Some data used for the research were obtained from THL Biobank. We thank all study participants for their generous participation at THL Biobank. Part of this work was conducted using the UK Biobank Resource under application number 24711. A full list of acknowledgments appears in Supplementary Note 3.
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