Afficher la notice abrégée

Antithrombin, PC (Protein C), and PS (Protein S): Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels

dc.rights.licenseopenen_US
dc.contributor.authorJI, Yuekai
dc.contributor.authorTEMPRANO-SAGRERA, Gerard
dc.contributor.authorHOLLE, Lori A.
dc.contributor.authorBEBO, Allison
dc.contributor.authorBRODY, Jennifer
dc.contributor.authorLE, Ngoc-Quynh
dc.contributor.authorKANGRO, Kadri
dc.contributor.authorBROWN, Michael R.
dc.contributor.authorMARTINEZ-PEREZ, Angel
dc.contributor.authorSITLANI, Colleen M.
dc.contributor.authorSUCHON, Pierre
dc.contributor.authorKLEBER, Marcus E.
dc.contributor.authorEMMERT, David B.
dc.contributor.authorBILGE OZEL, Ayse
dc.contributor.authorDOBSON, Dre'Von A.
dc.contributor.authorTANG, Weihong
dc.contributor.authorLLOBET, Dolors
dc.contributor.authorTRACY, Russell P
dc.contributor.authorDELEUZE, Jean-Francois
dc.contributor.authorDELGADO, Graciela E.
dc.contributor.authorGOGELE, Martin
dc.contributor.authorWIGGINS, Kerri L.
dc.contributor.authorSOUTO, Juan Carlos
dc.contributor.authorPANKOW, James S.
dc.contributor.authorTAYLOR, Kent D.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorMOISSL, Angela P.
dc.contributor.authorFUCHSBERGER, Christian
dc.contributor.authorROSENDAAL, Frits R.
dc.contributor.authorMORRISON, Alanna C.
dc.contributor.authorSORIA, Jose Manuel
dc.contributor.authorCUSHMAN, Mary
dc.contributor.authorMORANGE, Pierre-Emmanuel
dc.contributor.authorMARZ, Winfried
dc.contributor.authorHICKS, Andrew A.
dc.contributor.authorDESCH, Karl C.
dc.contributor.authorJOHNSON, Andrew D.
dc.contributor.authorDE VRIES, Paul S.
dc.contributor.authorWOLBERG, Alisa S.
dc.contributor.authorSMITH, Nicholas L.
dc.contributor.authorSABATER-LLEAL, Maria
dc.date.accessioned2023-05-15T07:32:42Z
dc.date.available2023-05-15T07:32:42Z
dc.date.issued2023-04-27
dc.identifier.issn1524-4636 (Electronic) 1079-5642 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182108
dc.description.abstractEnBACKGROUND: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total. METHODS: Study participants were of European and African ancestries, and genotype data were imputed to TOPMed, a dense multiancestry reference panel. Each of the 10 studies conducted a genome-wide association studies for each phenotype and summary results were meta-analyzed, stratified by ancestry. Analysis of AT included 25 243 European ancestry and 2688 African ancestry participants, PC analysis included 16 597 European ancestry and 2688 African ancestry participants, PSF and PST analysis included 4113 and 6409 European ancestry participants. We also conducted transcriptome-wide association analyses and multiphenotype analysis to discover additional associations. Novel genome-wide association studies and transcriptome-wide association analyses findings were validated by in vitro functional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes. RESULTS: Genome-wide association studies meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (GCKR, BAZ1B, and HP-TXNL4B) and 1 with PS levels (ORM1-ORM2). transcriptome-wide association analyses identified 3 newly associated genes: 1 with antithrombin level (FCGRT), 1 with PC (GOLM2), and 1 with PS (MYL7). In addition, we replicated 7 independent loci reported in previous studies. Functional experiments provided evidence for the involvement of GCKR, SNX17, and HP genes in antithrombin regulation. CONCLUSIONS: The use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels.
dc.language.isoENen_US
dc.subject.enAntithrombin
dc.subject.enAging
dc.subject.enHemostasis
dc.subject.enAnticoagulant
dc.subject.enGenotype
dc.title.enAntithrombin, PC (Protein C), and PS (Protein S): Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels
dc.title.alternativeArterioscler Thromb Vasc Biolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/atvbaha.122.318213en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37128921en_US
bordeaux.journalArteriosclerosis, Thrombosis, and Vascular Biologyen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04097189
hal.version1
hal.date.transferred2023-05-15T07:33:12Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Arteriosclerosis,%20Thrombosis,%20and%20Vascular%20Biology&rft.date=2023-04-27&rft.eissn=1524-4636%20(Electronic)%201079-5642%20(Linking)&rft.issn=1524-4636%20(Electronic)%201079-5642%20(Linking)&rft.au=JI,%20Yuekai&TEMPRANO-SAGRERA,%20Gerard&HOLLE,%20Lori%20A.&BEBO,%20Allison&BRODY,%20Jennifer&rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée