Genome-wide association meta-analysis of ...
Document type :
Article dans une revue scientifique: Article original
Title :
Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
Author(s) :
Di Castelnuovo, Augusto [Auteur]
Bonaccio, Marialaura [Auteur]
Costanzo, Simona [Auteur]
Mcelduff, Patrick [Auteur]
Linneberg, Allen [Auteur]
Salomaa, Veikko [Auteur]
Männistö, Satu [Auteur]
Ferrières, Jean [Auteur]
Dallongeville, Jean [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Thorand, Barbara [Auteur]
Brenner, Hermann [Auteur]
Ferrario, Marco [Auteur]
Veronesi, Giovanni [Auteur]
Tamosiunas, Abdonas [Auteur]
Grimsgaard, Sameline [Auteur]
Drygas, Wojciech [Auteur]
Malyutina, Sofia [Auteur]
Söderberg, Stefan [Auteur]
Nordendahl, Maria [Auteur]
Kee, Frank [Auteur]
Grassi, Guido [Auteur]
Dabboura, Salim [Auteur]
Borchini, Rossana [Auteur]
Westermann, Dirk [Auteur]
Schrage, Benedikt [Auteur]
Zeller, Tanja [Auteur]
Kuulasmaa, Kari [Auteur]
Blankenberg, Stefan [Auteur]
Donati, Maria Benedetta [Auteur]
Iacoviello, Licia [Auteur]
de Gaetano, Giovanni [Auteur]
Bonaccio, Marialaura [Auteur]
Costanzo, Simona [Auteur]
Mcelduff, Patrick [Auteur]
Linneberg, Allen [Auteur]
Salomaa, Veikko [Auteur]
Männistö, Satu [Auteur]
Ferrières, Jean [Auteur]
Dallongeville, Jean [Auteur]

Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Thorand, Barbara [Auteur]
Brenner, Hermann [Auteur]
Ferrario, Marco [Auteur]
Veronesi, Giovanni [Auteur]
Tamosiunas, Abdonas [Auteur]
Grimsgaard, Sameline [Auteur]
Drygas, Wojciech [Auteur]
Malyutina, Sofia [Auteur]
Söderberg, Stefan [Auteur]
Nordendahl, Maria [Auteur]
Kee, Frank [Auteur]
Grassi, Guido [Auteur]
Dabboura, Salim [Auteur]
Borchini, Rossana [Auteur]
Westermann, Dirk [Auteur]
Schrage, Benedikt [Auteur]
Zeller, Tanja [Auteur]
Kuulasmaa, Kari [Auteur]
Blankenberg, Stefan [Auteur]
Donati, Maria Benedetta [Auteur]
Iacoviello, Licia [Auteur]
de Gaetano, Giovanni [Auteur]
Journal title :
Nature Genetics
Pages :
964-972
Publisher :
Nature Publishing Group
Publication date :
2023-06
ISSN :
1061-4036
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular ...
Show more >Abstract Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3 , which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.Show less >
Show more >Abstract Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3 , which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
ANR Project :
Collections :
Source :
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