TY - JOUR
T1 - Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
AU - Steinthorsdottir, Valgerdur
AU - McGinnis, Ralph
AU - Williams, Nicholas O.
AU - Stefansdottir, Lilja
AU - Thorleifsson, Gudmar
AU - Shooter, Scott
AU - Fadista, Joao
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 - Gretasdottir, 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 - FINNPEC Consortium
AU - Laivuori, Hannele
AU - Heinonen, Seppo
AU - Kajantie, Eero
AU - Kere, Juha
AU - Kivinen, Katja
AU - Pouta, Anneli
PY - 2020/12/25
Y1 - 2020/12/25
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. 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.
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. 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.
KW - BODY-MASS INDEX
KW - CARDIOVASCULAR-DISEASE
KW - COHORT PROFILE
KW - FETAL
KW - GENOME-WIDE ASSOCIATION
KW - MEDICAL BIRTH REGISTRY
KW - METAANALYSIS
KW - PREGNANCY
KW - RISK
KW - VARIANTS
KW - 3123 Gynaecology and paediatrics
U2 - 10.1038/s41467-020-19733-6
DO - 10.1038/s41467-020-19733-6
M3 - Article
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5976
ER -