Exploitation of genomic variants affecting coronary artery disease and stroke risk for therapeutic intervention

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Project Title: Exploitation of genomic variants affecting coronary artery disease and stroke risk for therapeutic intervention
Project Number: CORDIS-110211
Project web address: Follow on CORDIS
Organization: Deutsches Herzzentrum Munchen, Germany, Munich
Collaborators: University Of Leicester, GB
The Chancellor, Masters And Scholars Of The University Of Oxford, GB
Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V., DE
Genedata Ag, CH
Universitair Medisch Centrum Utrecht, NL
Clinical Gene Networks Ab, SE
Universitat Zu Lubeck, DE
European Screeningport Gmbh, DE
Horizon Discovery Limited, GB
4Sc Discovery Gmbh, DE
Bioceros Bv, NL
Principal Investigators (PI): Johan Björkegren, SE
Stephen Conway, GB
Marie Adams, GB
Per Larsen, DE
Timo Wittenberger, CH
Michael Prestele, DE
Philip Gribbon, DE
Karin Krol-Simons, NL
Stefan Strobl, DE
Dirk Gewert, GB
Remco Brandt, NL
Martin Dichgans, DE
Nadine Clausen, DE
 
Project Description:
Atherosclerosis and its most disabling sequelae, coronary artery disease (CAD) and stroke, are leading causes of death in Europe. Until now, preventive and therapeutic interventions for these diseases aim at ameliorating the effects of established cardiovascular risk factors. More recently, results of genome-wide association (GWA) studies added to our perception of mechanisms leading to atherosclerosis. At present, over 40 CAD and several genomic risk loci have been identified, the majority through efforts led by the applicants. Some genes at these loci work through known risk factors such as lipids and, in fact, are already established or evolving treatment targets. However, this is not true for the majority of risk variants, which implies that key pathways leading to atherosclerosis are yet to be exploited for therapeutic intervention. This EU network (CVgenes@target), which brings together an equal number of SME- and academic partners, will utilize genomic variants affecting atherosclerosis risk for identification of both underlying genes and affected pathways in order to identify, characterize, and validate novel therapeutically relevant targets for prevention and treatment of CAD and stroke. In programme 1 we will investigate molecular mechanisms at the genomic loci in order to further unravel causal genes, in programme 2 we will explore in vitro and in vivo whether the pathways disturbed by causal genes are suitable for therapeutic intervention, and in programme 3 we will establish assays and initiate high throughput screens to tackle therapeutically attractive targets. Our resources including large OMICs and state-of-the-art bioinformatics platforms as well as multiple, already established in vitro and in vivo models support the feasibility of the approach. In fact, two genomic risk loci (ADAMTS7 (CAD); HDAC9 (stroke and CAD)), both identified in GWA studies under direction of the applicants, already revealed attractive targets for therapeutic intervention.
 
Project Terms:
life sciences