EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD000100012110EGA dataset EGAD00010001211EGAPreeclampsia, 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.Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.McGinnis Ralph R, Steinthorsdottir Valgerdur V, Williams Nicholas O NO, Thorleifsson Gudmar G, Shooter Scott S, Hjartardottir Sigrun S, Bumpstead Suzannah S, Stefansdottir Lilja L, Hildyard Lucy L, Sigurdsson Jon K JK, Kemp John P JP, Silva Gabriela B GB, Thomsen Liv Cecilie V LCV, Jääskeläinen Tiina T, Kajantie Eero E, Chappell Sally S, Kalsheker Noor N, Moffett Ashley A, Hiby Susan S, Lee Wai Kwong WK, Padmanabhan Sandosh S, Simpson Nigel A B NAB, Dolby Vivien A VA, Staines-Urias Eleonora E, Engel Stephanie M SM, Haugan Anita A, Trogstad Lill L, Svyatova Gulnara G, Zakhidova Nodira N, Najmutdinova Dilbar D, Dominiczak Anna F AF, Gjessing Håkon K HK, Casas Juan P JP, Dudbridge Frank F, Walker James J JJ, Pipkin Fiona Broughton FB, Thorsteinsdottir Unnur U, Geirsson Reynir T RT, Lawlor Debbie A DA, Iversen Ann-Charlotte AC, Magnus Per P, Laivuori Hannele H, Stefansson Kari K, Morgan Linda Lfalsepe_meta_20170131Inverse variance weighted fixed effect meta-analysis of three European GWAS studies of the offspring of Pre-eclampsia affected births (2658 Cases and 308267 Controls).2020-09-10 11:02:49EGAD00010001211960628628106EGAC00001000205EGAS00001001048