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

To access publisher's full text version of this article click on the hyperlink belowPreeclampsia, 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.European Union Wellcome Trust UK Medical Research Council European Research Council British Heart Foundation Norwegian Ministry of Health and Care Services Ministry of Education and Research NIH/NIEHS NIH/NINDS NICHD Jane and Aatos Erkko Foundation Paivikki and Sakari Sohlberg Foundation Academy of Finland University of Helsinki Hospital District of Helsinki and Uusimaa Novo Nordisk Foundation Finnish Foundation for Pediatric Research Emil Aaltonen Foundation Sigrid Juselius Foundation Research Council of Norway Liaison Committe