Utilising myocardial infarction genes for better treatment (druggable-MI-genes)
Description: Only one-third of the 90 loci identified for coronary artery disease (CAD) through genome-wide association studies (GWAS) are associated with traditional cardiovascular risk factors indicating that our understanding of mechanisms leading to atherosclerosis is substantially incomplete. Our consortium aims to unravel molecular alterations of loci shown by GWAS to increase CAD risk, but are currently not addressed for prevention and therapy. By integrating multi-tissue gene expression and RNA-sequence from several studies (e.g., STARNET) with the globally leading consortium of GWAS on CAD (CARDIoGRAM), we will first identify genes/transcripts underlying genetic risk variants of both myocardial infarction (i.e., unstable plaques) and stable CAD. Next, we will identify molecular contexts of these genes/transcripts in target tissues/cell-types, gene-networks and pathways within these; aiming to identify so-called key disease drivers. Furthermore, molecular mechanisms of plaque stability/instability already partly characterized by the applicants will be further scrutinized for options of therapeutic interventions. Finally, translation to human pathophysiology will be achieved by interrogating unique biobanks of human atherosclerotic plaque material as well as population-based samples of up to 500,000 individuals with genome-wide data and in-depth phenotypic characterization for better recognition of individuals at risk. The overall aim of druggable-MI-genes is to lay the foundation for a more precise and genomics-based prevention of coronary atherosclerosis and plaque stability.
Funder: Eesti Teadusagentuur
Amount: €145,400
Funding type: grant
Funder scheme: Mobilitas Pluss ERA-NET support
Start date: 2018-09-01
End date: 2022-08-31
Investigator: Andres Metspalu
Institution: University of Tartu, Institute of Genomics
Funded outputs count: 2
Funder award ID: MOBERA15
OpenAlex ID: G6024987315