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

FINNPEC Consortium; GOPEC Consortium; 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; Hannele Laivuori

doi:10.1038/s41467-020-19733-6

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

FINNPEC Consortium
, GOPEC Consortium
, 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, Hannele Laivuori

Research output: Contribution to journal › Article › Scientific › peer-review

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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
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19733-6
Publication status	Published - 25 Nov 2020
Publication type	A1 Journal article-refereed

Keywords

Adaptor Proteins, Signal Transducing/genetics
Adult
Aged
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
Asia, Central/epidemiology
Blood Pressure/genetics
Case-Control Studies
Datasets as Topic
Europe/epidemiology
Female
Fibroblast Growth Factor 5/genetics
Genetic Loci/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Hypertension, Pregnancy-Induced/epidemiology
MDS1 and EVI1 Complex Locus Protein/genetics
Middle Aged
Multifactorial Inheritance
Pre-Eclampsia/epidemiology
Pregnancy
Prospective Studies

Publication forum classification

Publication forum level 3

Access to Document

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

s41467-020-19733-6Final published version, 1.62 MBLicence: CC BY

http://urn.fi/URN:NBN:fi:tuni-202101171392Licence: CC BY

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FINNPEC Consortium, GOPEC Consortium, 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., ... Laivuori, H. (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

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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.",

keywords = "Adaptor Proteins, Signal Transducing/genetics, Adult, Aged, Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics, Asia, Central/epidemiology, Blood Pressure/genetics, Case-Control Studies, Datasets as Topic, Europe/epidemiology, Female, Fibroblast Growth Factor 5/genetics, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Pregnancy-Induced/epidemiology, MDS1 and EVI1 Complex Locus Protein/genetics, Middle Aged, Multifactorial Inheritance, Pre-Eclampsia/epidemiology, Pregnancy, Prospective Studies",

author = "\{FINNPEC Consortium\} and \{GOPEC Consortium\} and 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 Maria-Carolina Borges 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 Hannele Laivuori",

year = "2020",

month = nov,

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doi = "10.1038/s41467-020-19733-6",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

FINNPEC Consortium, GOPEC Consortium, Steinthorsdottir, V, McGinnis, R, Williams, NO, Stefansdottir, L, Thorleifsson, G, Shooter, S, Fadista, J, Sigurdsson, JK, Auro, KM, Berezina, G, Borges, M-C, 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 & Laivuori, H 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

TY - JOUR

T1 - Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

AU - FINNPEC Consortium

AU - GOPEC Consortium

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 - Poston, Lucilla

AU - Prescott, Gordon

AU - Laivuori, Hannele

PY - 2020/11/25

Y1 - 2020/11/25

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.

KW - Adaptor Proteins, Signal Transducing/genetics

KW - Adult

KW - Aged

KW - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics

KW - Asia, Central/epidemiology

KW - Blood Pressure/genetics

KW - Case-Control Studies

KW - Datasets as Topic

KW - Europe/epidemiology

KW - Female

KW - Fibroblast Growth Factor 5/genetics

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Hypertension, Pregnancy-Induced/epidemiology

KW - MDS1 and EVI1 Complex Locus Protein/genetics

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Pre-Eclampsia/epidemiology

KW - Pregnancy

KW - Prospective Studies

U2 - 10.1038/s41467-020-19733-6

DO - 10.1038/s41467-020-19733-6

M3 - Article

C2 - 33239696

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5976

ER -

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

Abstract

Keywords

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