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; Line Skotte; Karina Meden Sørensen; Juha Kere; FINNPEC Consortium; GOPEC Consortium

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, Line Skotte, Karina Meden Sørensen, Juha Kere, FINNPEC Consortium, GOPEC Consortium

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

128 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	5976
Tidsskrift	Nature Communications
Vol/bind	11
Udgave nummer	1
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-020-19733-6
Status	Udgivet - 2020

Adgang til dokumentet

10.1038/s41467-020-19733-6Licens: CC BY

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian womenForlagets udgivne version, 1,6 MBLicens: CC BY

Citationsformater

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., ... GOPEC Consortium (2020). Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nature Communications, 11(1), Artikel 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, Skotte, L, Sørensen, KM, Kere, J, FINNPEC Consortium & GOPEC Consortium 2020, 'Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women', Nature Communications, bind 11, nr. 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.",

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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

AU - Kemp, John P.

AU - Kivinen, Katja

AU - Klungsøyr, Kari

AU - Lee, Wai K.

AU - Melbye, Mads

AU - Miedzybrodska, Zosia

AU - Moffett, Ashley

AU - Najmutdinova, Dilbar

AU - Nishanova, Firuza

AU - Olafsdottir, Thorunn

AU - Perola, Markus

AU - Pipkin, Fiona Broughton

AU - Skotte, Line

AU - Sørensen, Karina Meden

AU - Kere, Juha

AU - FINNPEC Consortium

AU - GOPEC Consortium

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-19733-6

DO - 10.1038/s41467-020-19733-6

M3 - Journal article

C2 - 33239696

AN - SCOPUS:85096579509

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5976

ER -