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Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

dc.rights.licenseopenen_US
dc.contributor.authorHARTIALA, Jaana A
dc.contributor.authorHAN, Yi
dc.contributor.authorJIA, Qiong
dc.contributor.authorHILSER, James R
dc.contributor.authorHUANG, Pin
dc.contributor.authorGUKASYAN, Janet
dc.contributor.authorSCHWARTZMAN, William S
dc.contributor.authorCAI, Zhiheng
dc.contributor.authorBISWAS, Subarna
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorSMITH, Nicholas L
dc.contributor.authorSELDIN, Marcus
dc.contributor.authorPAN, Calvin
dc.contributor.authorMEHRABIAN, Margarete
dc.contributor.authorLUSIS, Aldons J
dc.contributor.authorBAZELEY, Peter
dc.contributor.authorSUN, Yan V
dc.contributor.authorLIU, Chang
dc.contributor.authorQUYYUMI, Arshed A
dc.contributor.authorSCHOLZ, Markus
dc.contributor.authorTHIERY, Joachim
dc.contributor.authorDELGADO, Graciela E
dc.contributor.authorKLEBER, Marcus E
dc.contributor.authorMÄRZ, Winfried
dc.contributor.authorHOWE, Laurence J
dc.contributor.authorASSELBERGS, Folkert W
dc.contributor.authorVAN VUGT, Marion
dc.contributor.authorVLACHOJANNIS, Georgios J
dc.contributor.authorPATEL, Riyaz S
dc.contributor.authorLYYTIKÄINEN, Leo-Pekka
dc.contributor.authorKÄHÖNEN, Mika
dc.contributor.authorLEHTIMÄKI, Terho
dc.contributor.authorNIEMINEN, Tuomo V M
dc.contributor.authorKUUKASJÄRVI, Pekka
dc.contributor.authorLAURIKKA, Jari O
dc.contributor.authorCHANG, Xuling
dc.contributor.authorHENG, Chew-Kiat
dc.contributor.authorJIANG, Rong
dc.contributor.authorKRAUS, William E
dc.contributor.authorHAUSER, Elizabeth R
dc.contributor.authorFERGUSON, Jane F
dc.contributor.authorREILLY, Muredach P
dc.contributor.authorITO, Kaoru
dc.contributor.authorKOYAMA, Satoshi
dc.contributor.authorKAMATANI, Yoichiro
dc.contributor.authorKOMURO, Issei
dc.contributor.authorSTOLZE, Lindsey K
dc.contributor.authorROMANOSKI, Casey E
dc.contributor.authorKHAN, Mohammad Daud
dc.contributor.authorTURNER, Adam W
dc.contributor.authorMILLER, Clint L
dc.contributor.authorAHERRAHROU, Redouane
dc.contributor.authorCIVELEK, Mete
dc.contributor.authorMA, Lijiang
dc.contributor.authorBJÖRKEGREN, Johan L M
dc.contributor.authorKUMAR, S Ram
dc.contributor.authorTANG, W H Wilson
dc.contributor.authorHAZEN, Stanley L
dc.contributor.authorALLAYEE, Hooman
dc.date.accessioned2021-03-31T14:21:41Z
dc.date.available2021-03-31T14:21:41Z
dc.date.issued2021-03-01
dc.identifier.issn1522-9645en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26843
dc.description.abstractEnWhile most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
dc.language.isoENen_US
dc.subject.enMyocardial infarction
dc.subject.enGenetic factors
dc.subject.enGenome-wide association study
dc.subject.enMeta-analysis
dc.subject.enSLC44A3
dc.title.enGenome-wide analysis identifies novel susceptibility loci for myocardial infarction.
dc.title.alternativeEur Heart Jen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/eurheartj/ehaa1040en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33532862en_US
bordeaux.journalEuropean Heart Journalen_US
bordeaux.page919-933en_US
bordeaux.volume42en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue9en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-03187064
hal.version1
hal.date.transferred2021-03-31T14:21:49Z
hal.exporttrue
workflow.import.sourcepubmed
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