Title |
Variants in the fetal genome near FLT1 are associated with risk of preeclampsia
|
---|---|
Published in |
Nature Genetics, June 2017
|
DOI | 10.1038/ng.3895 |
Pubmed ID | |
Authors |
Ralph McGinnis, Valgerdur Steinthorsdottir, Nicholas O Williams, Gudmar Thorleifsson, Scott Shooter, Sigrun Hjartardottir, Suzannah Bumpstead, Lilja Stefansdottir, Lucy Hildyard, Jon K Sigurdsson, John P Kemp, Gabriela B Silva, Liv Cecilie V Thomsen, Tiina Jääskeläinen, Eero Kajantie, Sally Chappell, Noor Kalsheker, Ashley Moffett, Susan Hiby, Wai Kwong Lee, Sandosh Padmanabhan, Nigel A B Simpson, Vivien A Dolby, Eleonora Staines-Urias, Stephanie M Engel, Anita Haugan, Lill Trogstad, Gulnara Svyatova, Nodira Zakhidova, Dilbar Najmutdinova, Anna F Dominiczak, Håkon K Gjessing, Juan P Casas, Frank Dudbridge, James J Walker, Fiona Broughton Pipkin, Unnur Thorsteinsdottir, Reynir T Geirsson, Debbie A Lawlor, Ann-Charlotte Iversen, Per Magnus, Hannele Laivuori, Kari Stefansson, Linda Morgan |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 31 | 28% |
United Kingdom | 15 | 13% |
Spain | 3 | 3% |
Switzerland | 3 | 3% |
Finland | 3 | 3% |
France | 2 | 2% |
Netherlands | 2 | 2% |
Canada | 2 | 2% |
Qatar | 1 | <1% |
Other | 8 | 7% |
Unknown | 42 | 38% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 56 | 50% |
Scientists | 38 | 34% |
Science communicators (journalists, bloggers, editors) | 10 | 9% |
Practitioners (doctors, other healthcare professionals) | 8 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Finland | 1 | <1% |
Unknown | 280 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 36 | 13% |
Student > Bachelor | 31 | 11% |
Researcher | 28 | 10% |
Student > Master | 28 | 10% |
Other | 15 | 5% |
Other | 49 | 17% |
Unknown | 94 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 65 | 23% |
Biochemistry, Genetics and Molecular Biology | 47 | 17% |
Agricultural and Biological Sciences | 24 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 2% |
Nursing and Health Professions | 5 | 2% |
Other | 29 | 10% |
Unknown | 105 | 37% |