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Title: Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.
Authors: McGinnis, R
Steinthorsdottir, V
Williams, NO
Thorleifsson, G
Shooter, S
Hjartardottir, S
Bumpstead, S
Stefansdottir, L
Hildyard, L
Sigurdsson, JK
Kemp, JP
Silva, GB
Thomsen, LCV
Jääskeläinen, T
Kajantie, E
Chappell, S
Kalsheker, N
Moffett, A
Hiby, S
Lee, WK
Padmanabhan, S
Simpson, NAB
Dolby, VA
Staines-Urias, E
Engel, SM
Haugan, A
Trogstad, L
Svyatova, G
Zakhidova, N
Najmutdinova, D
FINNPEC Consortium
GOPEC Consortium
Dominiczak, AF
Gjessing, HK
Casas, JP
Dudbridge, Frank
Walker, JJ
Pipkin, FB
Thorsteinsdottir, U
Geirsson, RT
Lawlor, DA
Iversen, A-C
Magnus, P
Laivuori, H
Stefansson, K
Morgan, L
First Published: 19-Jun-2017
Publisher: Nature Publishing Group
Citation: Nature Genetics, 2017, 49 (8), pp. 1255–1260
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.
DOI Link: 10.1038/ng.3895
ISSN: 1061-4036
eISSN: 1546-1718
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Nature America Inc., part of Springer Nature. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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