Maqola

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

Ralph McGinnisWellcome Trust Sanger Institute,Cambridge,UKValgerður SteinthórsdóttirdeCODE genetics/AMGEN, Reykjavik, Iceland;Nicholas WilliamsWellcome Trust Sanger Institute,Cambridge,UKGuðmar ÞorleifssondeCODE genetics/AMGEN, Reykjavik, Iceland;Scott ShooterWellcome Trust Sanger Institute,Cambridge,UKSigrun HjartardottirDepartment of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, IcelandSuzannah BumpsteadWellcome Trust Sanger Institute,Cambridge,UKLilja StefánsdóttirdeCODE genetics/AMGEN, Reykjavik, Iceland;Lucy HildyardWellcome Trust Sanger Institute,Cambridge,UKJon K. SigurdssondeCODE genetics/AMGEN, Reykjavik, Iceland;John P. KempMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UKGabriela B. SilvaCentre of Molecular Inflammation Research (CEMIR) and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayLiv Cecilie Vestrheim ThomsenCentre of Molecular Inflammation Research (CEMIR) and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayTiina JääskeläinenMedical and Clinical genetics, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandEero KajantieChildren's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandSally ChappellSchool of Life Sciences; University of Nottingham; Nottingham UKNoor KalshekerSchool of Life Sciences; University of Nottingham; Nottingham UKAshley MoffettDepartment of Pathology University of Cambridge Cambridge UKSusan E. HibyDepartment of Pathology University of Cambridge Cambridge UKWai LeeBHF Glasgow Cardiovascular Research Centre; Institute of Cardiovascular and Medical Sciences; University of Glasgow Glasgow UKSandosh PadmanabhanBHF Glasgow Cardiovascular Research Centre; Institute of Cardiovascular and Medical Sciences; University of Glasgow Glasgow UKNigel SimpsonLeeds Institute of Biomedical and Clinical Sciences; University of Leeds; Leeds UKVivien A. DolbyLeeds Institute of Biomedical and Clinical Sciences; University of Leeds; Leeds UKEleonora Staines-UriasDepartment of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UKStephanie M. EngelDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA;A. HauganNorwegian Institute of Public Health , Oslo, NorwayLill TrogstadNorwegian Institute of Public Health , Oslo, NorwayGulnara SvyatovaScientific Center of Obstetrics, Gynecology and Perinatology, Almaty, KazakhstanNodira ZakhidovaInstitute of Immunology, Uzbek Academy of Sciences, Tashkent, UzbekistanDilbar NajmutdinovaRepublic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology, Tashkent, UzbekistanAnna F. DominiczakBHF Glasgow Cardiovascular Research Centre; Institute of Cardiovascular and Medical Sciences; University of Glasgow Glasgow UKHåkon K. GjessingDepartment of Global Public Health and Primary Care University of Bergen Bergen NorwayJuan P. CasasFarr Institute of Health Informatics, University College London, London, UKFrank DudbridgeDepartment of Non‐Communicable Disease Epidemiology London School of Hygiene & Tropical Medicine London UKJames J. WalkerLeeds Institute of Biomedical and Clinical Sciences; University of Leeds; Leeds UKFiona Broughton PipkinMedical School, University of Nottingham, Nottingham, UKUnnur ÞorsteinsdóttirdeCODE Genetics/Amgen, Reykjavik, IcelandReynir Tómas GeirssonDepartment of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, IcelandDebbie A. LawlorSchool of Social and Community Medicine, University of Bristol, Bristol, UKAnn‐Charlotte IversenCentre of Molecular Inflammation Research (CEMIR) and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayPer MagnusNorwegian Institute of Public Health , Oslo, NorwayHannele LaivuoriObstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandKāri StefánssondeCODE Genetics/Amgen, Reykjavik, IcelandLinda MorganSchool of Life Sciences; University of Nottingham; Nottingham UK

Carolina Digital Repository (University of North Carolina at Chapel Hill)repository2017en

ABI

Annotatsiya

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.

Hali tarjima qilinmagan

Mavzular

Pregnancy and preeclampsia studies Birth, Development, and Health RNA modifications and cancer

Identifikatorlar

DOI: 10.17615/d6cb-vs50

Iqtiboslar va manbalar

0 ta iqtibos0 ta foydalanilgan manba

Koʻrsatkichlar — AkademScholar · Tez orada