Show simple item record

dc.contributor.authorThibord, Florian
dc.contributor.authorKlarin, Derek
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorChen, Ming-Huei
dc.contributor.authorLevin, Michael G.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorGoode, Ellen L.
dc.contributor.authorHveem, Kristian
dc.contributor.authorTeder-Laving, Maris
dc.contributor.authorMartinez-Perez, Angel
dc.contributor.authorAïssi, Dylan
dc.contributor.authorDaian-Bacq, Delphine
dc.contributor.authorIto, Kaoru
dc.contributor.authorNatarajan, Pradeep
dc.contributor.authorLutsey, Pamela L.
dc.contributor.authorNadkarni, Girish N.
dc.contributor.authorde Vries, Paul S.
dc.contributor.authorCuellar-Partida, Gabriel
dc.contributor.authorWolford, Brooke N.
dc.contributor.authorPattee, Jack W.
dc.contributor.authorKooperberg, Charles
dc.contributor.authorBrækkan, Sigrid Kufaas
dc.contributor.authorLi-Gao, Ruifang
dc.contributor.authorSaut, Noemie
dc.contributor.authorSept, Corriene
dc.contributor.authorGermain, Marine
dc.contributor.authorJudy, Renae L.
dc.contributor.authorWiggins, Kerri L.
dc.contributor.authorKo, Darae
dc.contributor.authorO'Donnell, Christopher J.
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorGiulianini, Franco
dc.contributor.authorDe Andrade, Mariza
dc.contributor.authorNøst, Therese Haugdahl
dc.contributor.authorBoland, Anne
dc.contributor.authorEmpana, Jean-Philippe
dc.contributor.authorKoyama, Satoshi
dc.contributor.authorGilliland, Thomas
dc.contributor.authorDo, Ron
dc.contributor.authorHuffman, Jennifer E.
dc.contributor.authorWang, Xin
dc.contributor.authorZhou, Wei
dc.contributor.authorManuel Soria, Jose
dc.contributor.authorCarlos Souto, Juan
dc.contributor.authorPankratz, Nathan
dc.contributor.authorHaessler, Jeffery
dc.contributor.authorHindberg, Kristian Dalsbø
dc.contributor.authorRosendaal, Frits R
dc.contributor.authorTurman, Constance
dc.contributor.authorOlaso, Robert
dc.contributor.authorKember, Rachel L.
dc.contributor.authorBartz, Traci M.
dc.contributor.authorLynch, Julie A.
dc.contributor.authorHeckbert, Susan R.
dc.contributor.authorArmasu, Sebastian M.
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorSmadja, David M.
dc.contributor.authorJouven, Xavier
dc.contributor.authorKomuro, Issei
dc.contributor.authorClapham, Katharine R.
dc.contributor.authorLoos, Ruth J F
dc.contributor.authorWiller, Cristen J.
dc.contributor.authorSabater-Lleal, Maria
dc.contributor.authorPankow, James S.
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorMorelli, Vania Maris
dc.contributor.authorRidker, Paul M.
dc.contributor.authorVlieg, Astrid van Hylckama
dc.contributor.authorDeleuze, Jean-François
dc.contributor.authorKraft, Peter
dc.contributor.authorRader, Daniel J.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorSkogholt, Anne Heidi
dc.contributor.authorEmmerich, Joseph
dc.contributor.authorSuchon, Pierre
dc.contributor.authorRich, Stephen S.
dc.contributor.authorVy, Ha My T
dc.contributor.authorTang, Weihong
dc.contributor.authorJackson, Rebecca D.
dc.contributor.authorHansen, John Bjarne
dc.contributor.authorMorange, Pierre-Emmanuel
dc.contributor.authorKabrhel, Christopher
dc.contributor.authorTrégouët, David-Alexandre
dc.contributor.authorDamrauer, Scott M.
dc.contributor.authorJohnson, Andrew D.
dc.contributor.authorSmith, Nicholas L.
dc.date.accessioned2023-03-22T11:51:25Z
dc.date.available2023-03-22T11:51:25Z
dc.date.issued2022
dc.description.abstract<p><i>Background:</i> Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. <p><i>Methods:</i> We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. <p><i>Results:</i> In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. <p><i>Conclusions:</i> Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.en_US
dc.identifier.citationThibord, Klarin, Brody, Chen, Levin, Chasman, Goode, Hveem, Teder-Laving, Martinez-Perez, Aïssi, Daian-Bacq, Ito, Natarajan, Lutsey, Nadkarni, de Vries, Cuellar-Partida, Wolford, Pattee, Kooperberg, Brækkan, Li-Gao, Saut, Sept, Germain, Judy, Wiggins, Ko, O'Donnell, Taylor, Giulianini, De Andrade, Nøst, Boland, Empana, Koyama, Gilliland, Do, Huffman, Wang, Zhou, Manuel Soria, Carlos Souto, Pankratz, Haessler, Hindberg, Rosendaal, Turman, Olaso, Kember, Bartz, Lynch, Heckbert, Armasu, Brumpton, Smadja, Jouven, Komuro, Clapham, Loos, Willer, Sabater-Lleal, Pankow, Reiner, Morelli, Ridker, Vlieg, Deleuze, Kraft, Rader, Psaty, Skogholt, Emmerich, Suchon, Rich, Vy, Tang, Jackson, Hansen, Morange, Kabrhel, Trégouët, Damrauer, Johnson, Smith. Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors. Circulation. 2022;146(16):1225-1242en_US
dc.identifier.cristinIDFRIDAID 2069112
dc.identifier.doi10.1161/CIRCULATIONAHA.122.059675
dc.identifier.issn0009-7322
dc.identifier.issn1524-4539
dc.identifier.urihttps://hdl.handle.net/10037/28815
dc.language.isoengen_US
dc.relation.journalCirculation
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleCross-Ancestry Investigation of Venous Thromboembolism Genomic Predictorsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)