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A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

dc.rights.licenseopenen_US
dc.contributor.authorDE VRIES, Paul S
dc.contributor.authorREVENTUN, Paula
dc.contributor.authorBROWN, Michael R
dc.contributor.authorHEATH, Adam S
dc.contributor.authorHUFFMAN, Jennifer E
dc.contributor.authorLE, Ngoc-Quynh
dc.contributor.authorBEBO, Allison
dc.contributor.authorBRODY, Jennifer A
dc.contributor.authorTEMPRANO-SAGRERA, Gerard
dc.contributor.authorRAFFIELD, Laura M
dc.contributor.authorOZEL, Ayse Bilge
dc.contributor.authorTHIBORD, Florian
dc.contributor.authorJAIN, Deepti
dc.contributor.authorLEWIS, Joshua P
dc.contributor.authorRODRIGUEZ, Benjamin A T
dc.contributor.authorPANKRATZ, Nathan
dc.contributor.authorTAYLOR, Kent D
dc.contributor.authorPOLASEK, Ozren
dc.contributor.authorCHEN, Ming-Huei
dc.contributor.authorYANEK, Lisa R
dc.contributor.authorCARRASQUILLA, German D
dc.contributor.authorMARIONI, Riccardo E
dc.contributor.authorKLEBER, Marcus E
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorYAO, Jie
dc.contributor.authorLI-GAO, Ruifang
dc.contributor.authorJOSHI, Peter K
dc.contributor.authorTROMPET, Stella
dc.contributor.authorMARTINEZ-PEREZ, Angel
dc.contributor.authorGHANBARI, Mohsen
dc.contributor.authorHOWARD, Tom E
dc.contributor.authorREINER, Alex P
dc.contributor.authorARVANITIS, Marios
dc.contributor.authorRYAN, Kathleen A
dc.contributor.authorBARTZ, Traci M
dc.contributor.authorRUDAN, Igor
dc.contributor.authorFARADAY, Nauder
dc.contributor.authorLINNEBERG, Allan
dc.contributor.authorEKUNWE, Lynette
dc.contributor.authorDAVIES, Gail
dc.contributor.authorDELGADO, Graciela E
dc.contributor.authorSUCHON, Pierre
dc.contributor.authorGUO, Xiuqing
dc.contributor.authorROSENDAAL, Frits R
dc.contributor.authorKLARIC, Lucija
dc.contributor.authorNOORDAM, Raymond
dc.contributor.authorVAN ROOIJ, Frank
dc.contributor.authorCURRAN, Joanne E
dc.contributor.authorWHEELER, Marsha M
dc.contributor.authorOSBURN, William O
dc.contributor.authorO'CONNELL, Jeffrey R
dc.contributor.authorBOERWINKLE, Eric
dc.contributor.authorBESWICK, Andrew
dc.contributor.authorPSATY, Bruce M
dc.contributor.authorKOLCIC, Ivana
dc.contributor.authorSOUTO, Juan Carlos
dc.contributor.authorBECKER, Lewis C
dc.contributor.authorHANSEN, Torben
dc.contributor.authorDOYLE, Margaret F
dc.contributor.authorHARRIS, Sarah E
dc.contributor.authorMOISSL, Angela P
dc.contributor.authorDELEUZE, Jean-François
dc.contributor.authorRICH, Stephen S
dc.contributor.authorVAN HYLCKAMA VLIEG, Astrid
dc.contributor.authorCAMPBELL, Harry
dc.contributor.authorSTOTT, David J
dc.contributor.authorSORIA, Jose Manuel
dc.contributor.authorDE MAAT, Moniek P M
dc.contributor.authorALMASY, Laura
dc.contributor.authorBRODY, Lawrence C
dc.contributor.authorAUER, Paul L
dc.contributor.authorMITCHELL, Braxton D
dc.contributor.authorBEN-SHLOMO, Yoav
dc.contributor.authorFORNAGE, Myriam
dc.contributor.authorHAYWARD, Caroline
dc.contributor.authorMATHIAS, Rasika A
dc.contributor.authorKILPELÄINEN, Tuomas O
dc.contributor.authorLANGE, Leslie A
dc.contributor.authorCOX, Simon R
dc.contributor.authorMÄRZ, Winfried
dc.contributor.authorMORANGE, Pierre-Emmanuel
dc.contributor.authorROTTER, Jerome I
dc.contributor.authorMOOK-KANAMORI, Dennis O
dc.contributor.authorWILSON, James F
dc.contributor.authorVAN DER HARST, Pim
dc.contributor.authorJUKEMA, J Wouter
dc.contributor.authorIKRAM, M Arfan
dc.contributor.authorBLANGERO, John
dc.contributor.authorKOOPERBERG, Charles
dc.contributor.authorDESCH, Karl C
dc.contributor.authorJOHNSON, Andrew D
dc.contributor.authorSABATER-LLEAL, Maria
dc.contributor.authorLOWENSTEIN, Charles J
dc.contributor.authorSMITH, Nicholas L
dc.contributor.authorMORRISON, Alanna C
dc.date.accessioned2024-09-18T09:01:25Z
dc.date.available2024-09-18T09:01:25Z
dc.date.issued2024-05-02
dc.identifier.issn1528-0020en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201648
dc.description.abstractEnCoagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10-9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enHumans
dc.subject.envon Willebrand Factor
dc.subject.enFactor VIII
dc.subject.enPolymorphism
dc.subject.enSingle Nucleotide
dc.subject.enHuman Umbilical Vein Endothelial Cells
dc.subject.enMendelian Randomization Analysis
dc.subject.enGenome-Wide Association Study
dc.subject.enThrombosis
dc.subject.enGenetic Association Studies
dc.subject.enMale
dc.subject.enEndothelial Cells
dc.subject.enFemale
dc.subject.enKininogens
dc.subject.enReceptors
dc.subject.enCell Surface
dc.subject.enCell Adhesion Molecules
dc.subject.enLectins
dc.subject.enC-Type
dc.title.enA genetic association study of circulating coagulation factor VIII and von Willebrand factor levels
dc.title.alternativeBlooden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/blood.2023021452en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38320121en_US
bordeaux.journalBlooden_US
bordeaux.page1845-1855en_US
bordeaux.volume143en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue18en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Heart, Lung, and Blood Instituteen_US
bordeaux.identifier.funderIDAmerican Heart Associationen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04701077
hal.version1
hal.date.transferred2024-09-18T09:01:34Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Blood&amp;rft.date=2024-05-02&amp;rft.volume=143&amp;rft.issue=18&amp;rft.spage=1845-1855&amp;rft.epage=1845-1855&amp;rft.eissn=1528-0020&amp;rft.issn=1528-0020&amp;rft.au=DE%20VRIES,%20Paul%20S&amp;REVENTUN,%20Paula&amp;BROWN,%20Michael%20R&amp;HEATH,%20Adam%20S&amp;HUFFMAN,%20Jennifer%20E&amp;rft.genre=article


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