Variants in the fetal genome near FLT1 are associated with risk of preeclampsia

McGinnis, Ralph, Steinthorsdottir, Valgerdur, Williams, Nicholas O., Thorleifsson, Gudmar, Shooter, Scott, Hjartardottir, Sigrun, Bumpstead, Suzannah, Stefansdottir, Lilja, Hildyard, Lucy, Sigurdsson, Jon K., Kemp, John P., Silva, Gabriela B., Thomsen, Liv Cecilie V., Jaaskelainen, Tiina, Kajantie-, Eero, Chappell, Sally, Kalsheker, Noor, Moffett, Ashley, Hiby, Susan, Lee, Wai Kwong, Padmanabhan, Sandosh, Simpson, Nigel A. B., Dolby, Vivien A., Staines-Urias, Eleonora, Engel, Stephanie M., Haugan, Anita, Trogstad, Lill, Svyatova, Gulnara, Zakhidova, Nodira, Najmutdinova, Dilbar, Dominiczak, Anna F., Gjessing, Hakon K., Casas, Juan P., Dudbridge, Frank, Walker, James J., Pipkin, Fiona Broughton, Thorsteinsdottir, Unnur, Geirsson, Reynir T., Lawlor, Debbie A., Iversen, Ann-Charlotte, Magnus, Per, Laivuori, Hannele, Stefansson, Kari and Morgan, Linda (2017) Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nature Genetics, 49 8: 1255-1260. doi:10.1038/ng.3895


Author McGinnis, Ralph
Steinthorsdottir, Valgerdur
Williams, Nicholas O.
Thorleifsson, Gudmar
Shooter, Scott
Hjartardottir, Sigrun
Bumpstead, Suzannah
Stefansdottir, Lilja
Hildyard, Lucy
Sigurdsson, Jon K.
Kemp, John P.
Silva, Gabriela B.
Thomsen, Liv Cecilie V.
Jaaskelainen, Tiina
Kajantie-, Eero
Chappell, Sally
Kalsheker, Noor
Moffett, Ashley
Hiby, Susan
Lee, Wai Kwong
Padmanabhan, Sandosh
Simpson, Nigel A. B.
Dolby, Vivien A.
Staines-Urias, Eleonora
Engel, Stephanie M.
Haugan, Anita
Trogstad, Lill
Svyatova, Gulnara
Zakhidova, Nodira
Najmutdinova, Dilbar
Dominiczak, Anna F.
Gjessing, Hakon K.
Casas, Juan P.
Dudbridge, Frank
Walker, James J.
Pipkin, Fiona Broughton
Thorsteinsdottir, Unnur
Geirsson, Reynir T.
Lawlor, Debbie A.
Iversen, Ann-Charlotte
Magnus, Per
Laivuori, Hannele
Stefansson, Kari
Morgan, Linda
Title Variants in the fetal genome near FLT1 are associated with risk of preeclampsia
Formatted title
Variants in the fetal genome near FLT1 are associated with risk of preeclampsia
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2017-08-01
Sub-type Article (original research)
DOI 10.1038/ng.3895
Open Access Status Not yet assessed
Volume 49
Issue 8
Start page 1255
End page 1260
Total pages 6
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Abstract Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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