Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
Steinthorsdottir, Valgerdur; McGinnis, Ralph; Williams, Nicholas O.; Stefansdottir, Lilja; Thorleifsson, Gudmar; Shooter, Scott; Fadista, Joao; Sigurdsson, Jon K.; Auro, Kirsi M.; Berezina, Galina; Borges, Maria-Carolina; Bumpstead, Suzannah; Bybjerg-Grauholm, Jonas; Colgiu, Irina; Dolby, Vivien A.; Dudbridge, Frank; Engel, Stephanie M.; Franklin, Christopher S.; Frigge, Michael L.; Frisbaek, Yr; Geirsson, Reynir T.; Geller, Frank; Gretarsdottir, Solveig; Gudbjartsson, Daniel F.; Harmon, Quaker; Hougaard, David Michael; Hegay, Tatyana; Helgadottir, Anna; Hjartardottir, Sigrun; Jaeaeskelaeinen, Tiina; Johannsdottir, Hrefna; Jonsdottir, Ingileif; Juliusdottir, Thorhildur; Kalsheker, Noor; Kasimov, Abdumadjit; Kemp, John P.; Kivinen, Katja; Klungsoyr, Kari; Lee, Wai K.; Melbye, Mads; Miedzybrodska, Zosia; Moffett, Ashley; Najmutdinova, Dilbar; Nishanova, Firuza; Olafsdottir, Thorunn; Perola, Markus; Pipkin, Fiona Broughton; Poston, Lucilla; Prescott, Gordon; Saevarsdottir, Saedis; Salimbayeva, Damilya; Scaife, Paula Juliet; Skotte, Line; Staines-Urias, Eleonora; Stefansson, Olafur A.; Sorensen, Karina Meden; Thomsen, Liv Cecilie Vestrheim; Tragante, Vinicius; Trogstad, Lill; Simpson, Nigel A. B.; Laivuori, Hannele; Morgan, Linda; Aripova, Tamara; Casas, Juan P.; Dominiczak, Anna F.; Walker, James J.; Thorsteinsdottir, Unnur; Iversen, Ann-Charlotte; Feenstra, Bjarke; Lawlor, Deborah A.; Boyd, Heather Allison; Magnus, Per; Laivuori, Hannele; Zakhidova, Nodira; Svyatova, Gulnara; Stefansson, Kari; Morgan, Linda; Laivuori, Hannele; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Morgan, Linda; Pipkin, Fiona Broughton; Kalsheker, Noor; Walker, James J.; Macphail, Sheila; Kilby, Mark; Habiba, Marwan; Williamson, Catherine; O'Shaughnessy, Kevin; O'Brien, Shaughn; Cameron, Alan; Redman, Christopher W. G.; Farrall, Martin; Caulfield, Mark; Dominiczak, Anna F. (2020-11-25)
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
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https://urn.fi/URN:NBN:fi-fe2021082343899
Tiivistelmä
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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