McGinnis, R;
Steinthorsdottir, V;
Williams, NO;
Thorleifsson, G;
Shooter, S;
Hjartardottir, S;
Bumpstead, S;
... Morgan, L; + view all
(2017)
Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.
Nature Genetics
, 49
(8)
pp. 1255-1260.
10.1038/ng.3895.
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Abstract
Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death1. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility2. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets3,4. 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 preeclampsia5. 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.
| Type: | Article |
|---|---|
| Title: | Variants in the fetal genome near FLT1 are associated with risk of preeclampsia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3895 |
| Publisher version: | http://doi.org/10.1038/ng.3895 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Genetic association study, Reproductive disorders |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1562550 |
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