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; FINNPEC Consortium; GOPEC Consortium; Tamara  Aripova; Juan P Casas; Anna 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; Linda Morgan

doi:10.1038/s41467-020-19733-6

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 FrisbaekReynir 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, FINNPEC Consortium, GOPEC Consortium, Tamara Aripova, Juan P Casas, Anna 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, Linda Morgan

^*Corresponding author for this work

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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.

Original language	English
Article number	5976
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19733-6
Publication status	Published - 25 Nov 2020

Bibliographical note

Funding Information:
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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Steinthorsdottir, V., McGinnis, R., Williams, N. O., Stefansdottir, L., Thorleifsson, G., Shooter, S., Fadista, J., Sigurdsson, J. K., Auro, K. M., Berezina, G., Borges, M. C., Bumpstead, S., Bybjerg-Grauholm, J., Colgiu, I., Dolby, V. A., Dudbridge, F., Engel, S. M., Franklin, C. S., Frigge, M. L., ... Morgan, L. (2020). Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nature Communications, 11(1), Article 5976. https://doi.org/10.1038/s41467-020-19733-6

Steinthorsdottir, V, McGinnis, R, Williams, NO, Stefansdottir, L, Thorleifsson, G, Shooter, S, Fadista, J, Sigurdsson, JK, Auro, KM, Berezina, G, Borges, MC, Bumpstead, S, Bybjerg-Grauholm, J, Colgiu, I, Dolby, VA, Dudbridge, F, Engel, SM, Franklin, CS, Frigge, ML, Frisbaek, Y, Geirsson, RT, Geller, F, Gretarsdottir, S, Gudbjartsson, DF, Harmon, Q, Hougaard, DM, Hegay, T, Helgadottir, A, Hjartardottir, S, Jääskeläinen, T, Johannsdottir, H, Jonsdottir, I, Juliusdottir, T, Kalsheker, N, Kasimov, A, Kemp, JP, Kivinen, K, Klungsøyr, K, Lee, WK, Melbye, M, Miedzybrodska, Z, Moffett, A, Najmutdinova, D, Nishanova, F, Olafsdottir, T, Perola, M, Pipkin, FB, Poston, L, Prescott, G, Saevarsdottir, S, Salimbayeva, D, Scaife, PJ, Skotte, L, Staines-Urias, E, Stefansson, OA, Sørensen, KM, Vestrheim Thomsen, LC, Tragante, V, Trogstad, L, Simpson, NAB, FINNPEC Consortium, GOPEC Consortium, Aripova, T, Casas, JP, Dominiczak, A, Walker, JJ, Thorsteinsdottir, U, Iversen, A-C, Feenstra, B, Lawlor, DA, Boyd, HA, Magnus, P, Laivuori, H, Zakhidova, N, Svyatova, G, Stefansson, K & Morgan, L 2020, 'Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women', Nature Communications, vol. 11, no. 1, 5976. https://doi.org/10.1038/s41467-020-19733-6

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title = "Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women",

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.",

author = "Valgerdur Steinthorsdottir and Ralph McGinnis and Williams, {Nicholas O.} and Lilja Stefansdottir and Gudmar Thorleifsson and Scott Shooter and Jo{\~a}o Fadista and Sigurdsson, {Jon K.} and Auro, {Kirsi M.} and Galina Berezina and Borges, {Maria Carolina} and Suzannah Bumpstead and Jonas Bybjerg-Grauholm and Irina Colgiu and Dolby, {Vivien A.} and Frank Dudbridge and Engel, {Stephanie M.} and Franklin, {Christopher S.} and Frigge, {Michael L.} and Yr Frisbaek and Geirsson, {Reynir T.} and Frank Geller and Solveig Gretarsdottir and Gudbjartsson, {Daniel F.} and Quaker Harmon and Hougaard, {David Michael} and Tatyana Hegay and Anna Helgadottir and Sigrun Hjartardottir and Tiina J{\"a}{\"a}skel{\"a}inen and Hrefna Johannsdottir and Ingileif Jonsdottir and Thorhildur Juliusdottir and Noor Kalsheker and Abdumadjit Kasimov and Kemp, {John P.} and Katja Kivinen and Kari Klungs{\o}yr and Lee, {Wai K.} and Mads Melbye and Zosia Miedzybrodska and Ashley Moffett and Dilbar Najmutdinova and Firuza Nishanova and Thorunn Olafsdottir and Markus Perola and Pipkin, {Fiona Broughton} and Lucilla Poston and Gordon Prescott and Saedis Saevarsdottir and Damilya Salimbayeva and Scaife, {Paula Juliet} and Line Skotte and Eleonora Staines-Urias and Stefansson, {Olafur A.} and S{\o}rensen, {Karina Meden} and {Vestrheim Thomsen}, {Liv Cecilie} and Vinicius Tragante and Lill Trogstad and Simpson, {Nigel A B} and {FINNPEC Consortium} and {GOPEC Consortium} and Tamara Aripova and Casas, {Juan P} and Anna Dominiczak and Walker, {James J} and Unnur Thorsteinsdottir and Ann-Charlotte Iversen and Bjarke Feenstra and Lawlor, {Deborah A} and Boyd, {Heather Allison} and Per Magnus and Hannele Laivuori and Nodira Zakhidova and Gulnara Svyatova and Kari Stefansson and Linda Morgan",

note = "Funding Information: 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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AU - Steinthorsdottir, Valgerdur

AU - McGinnis, Ralph

AU - Williams, Nicholas O.

AU - Stefansdottir, Lilja

AU - Thorleifsson, Gudmar

AU - Shooter, Scott

AU - Fadista, João

AU - Sigurdsson, Jon K.

AU - Auro, Kirsi M.

AU - Berezina, Galina

AU - Borges, Maria Carolina

AU - Bumpstead, Suzannah

AU - Bybjerg-Grauholm, Jonas

AU - Colgiu, Irina

AU - Dolby, Vivien A.

AU - Dudbridge, Frank

AU - Engel, Stephanie M.

AU - Franklin, Christopher S.

AU - Frigge, Michael L.

AU - Frisbaek, Yr

AU - Geirsson, Reynir T.

AU - Geller, Frank

AU - Gretarsdottir, Solveig

AU - Gudbjartsson, Daniel F.

AU - Harmon, Quaker

AU - Hougaard, David Michael

AU - Hegay, Tatyana

AU - Helgadottir, Anna

AU - Hjartardottir, Sigrun

AU - Jääskeläinen, Tiina

AU - Johannsdottir, Hrefna

AU - Jonsdottir, Ingileif

AU - Juliusdottir, Thorhildur

AU - Kalsheker, Noor

AU - Kasimov, Abdumadjit

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AU - Klungsøyr, Kari

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AU - Najmutdinova, Dilbar

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AU - Olafsdottir, Thorunn

AU - Perola, Markus

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AU - Poston, Lucilla

AU - Prescott, Gordon

AU - Saevarsdottir, Saedis

AU - Salimbayeva, Damilya

AU - Scaife, Paula Juliet

AU - Skotte, Line

AU - Staines-Urias, Eleonora

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AU - Sørensen, Karina Meden

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AU - Tragante, Vinicius

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AU - Simpson, Nigel A B

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AU - Aripova, Tamara

AU - Casas, Juan P

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AU - Walker, James J

AU - Thorsteinsdottir, Unnur

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AU - Feenstra, Bjarke

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AU - Zakhidova, Nodira

AU - Svyatova, Gulnara

AU - Stefansson, Kari

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

Abstract

Bibliographical note

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

Abstract

Bibliographical note

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Fingerprint

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Aberdeen Maternity and Neonatal Databank

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Grampian Data Safe Haven (DaSH)

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