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Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism

dc.rights.licenseopenen_US
dc.contributor.authorLINDSTROM, S.
dc.contributor.authorWANG, L.
dc.contributor.authorSMITH, E. N.
dc.contributor.authorGORDON, W.
dc.contributor.authorVAN HYLCKAMA VLIEG, A.
dc.contributor.authorDE ANDRADE, M.
dc.contributor.authorBRODY, J. A.
dc.contributor.authorPATTEE, J. W.
dc.contributor.authorHAESSLER, J.
dc.contributor.authorBRUMPTON, B. M.
dc.contributor.authorCHASMAN, D. I.
dc.contributor.authorSUCHON, P.
dc.contributor.authorCHEN, M. H.
dc.contributor.authorTURMAN, C.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorGERMAIN, Marine
dc.contributor.authorWIGGINS, K. L.
dc.contributor.authorMACDONALD, J.
dc.contributor.authorBRAEKKAN, S. K.
dc.contributor.authorARMASU, S. M.
dc.contributor.authorPANKRATZ, N.
dc.contributor.authorJACKSON, R. D.
dc.contributor.authorNIELSEN, J. B.
dc.contributor.authorGIULIANINI, F.
dc.contributor.authorPUURUNEN, M. K.
dc.contributor.authorIBRAHIM, M.
dc.contributor.authorHECKBERT, S. R.
dc.contributor.authorDAMRAUER, S. M.
dc.contributor.authorNATARAJAN, P.
dc.contributor.authorKLARIN, D.
dc.contributor.authorDE VRIES, P. S.
dc.contributor.authorSABATER-LLEAL, M.
dc.contributor.authorHUFFMAN, J. E.
dc.contributor.authorBAMMLER, T. K.
dc.contributor.authorFRAZER, K. A.
dc.contributor.authorMCCAULEY, B. M.
dc.contributor.authorTAYLOR, K.
dc.contributor.authorPANKOW, J. S.
dc.contributor.authorREINER, A. P.
dc.contributor.authorGABRIELSEN, M. E.
dc.contributor.authorDELEUZE, J. F.
dc.contributor.authorO'DONNELL, C. J.
dc.contributor.authorKIM, J.
dc.contributor.authorMCKNIGHT, B.
dc.contributor.authorKRAFT, P.
dc.contributor.authorHANSEN, J. B.
dc.contributor.authorROSENDAAL, F. R.
dc.contributor.authorHEIT, J. A.
dc.contributor.authorPSATY, B. M.
dc.contributor.authorTANG, W.
dc.contributor.authorKOOPERBERG, C.
dc.contributor.authorHVEEM, K.
dc.contributor.authorRIDKER, P. M.
dc.contributor.authorMORANGE, P. E.
dc.contributor.authorJOHNSON, A. D.
dc.contributor.authorKABRHEL, C.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorSMITH, N. L.
dc.date.accessioned2020-06-26T07:25:59Z
dc.date.available2020-06-26T07:25:59Z
dc.date.issued2019-11-07
dc.identifier.issn0006-4971en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/8205
dc.description.abstractEnVenous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.
dc.language.isoENen_US
dc.subject.enVINTAGE
dc.title.enGenomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism
dc.title.alternativeBlooden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/blood.2019000435en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31420334en_US
bordeaux.journalBlooden_US
bordeaux.page1645-1657en_US
bordeaux.volume134en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue19en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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