McGinnis, R, Steinthorsdottir, V, Williams, NO et al. (43 more authors) (2017) Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nature Genetics, 49. pp. 1255-1260. ISSN 1061-4036
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Obstetrics & Gynaecology (Leeds) |
Funding Information: | Funder Grant number EU - European Union 282540 |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jul 2017 14:21 |
Last Modified: | 21 Aug 2017 13:36 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/ng.3895 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119176 |