Project: Utilising myocardial infarction genes for better treatment

Acronym	druggable-MI-genes (Reference Number: 2. JTC-2017_40)
Project Topic	Genome-wide association studies (GWAS) firmly associated 93 loci with coronary artery disease (CAD) risk. The mechanisms leading to a higher burden of coronary atherosclerosis are unclear at most loci. Our consortium aims to unravel molecular alterations of genetic variants shown by GWAS to increase CAD risk, but are currently not addressed for prevention or therapy. By exploring loci from the globally leading GWAS consortium on CAD (CARDIoGRAM) for expression signals in multi-tissue transcriptomics (RNA-seq) data from several studies (e.g., STARNET, Athero-Express™), we will first differentiate between genes/ transcripts underlying genetic risk of myocardial infarction (i.e., unstable plaques) vs. stable CAD. Next, we will explore molecular contexts of the most promising candidates in tissue-specific co-expression networks and pathways, aiming to identify the so-called key disease drivers (WP1). In parallel, novel molecular mechanisms of plaque instability, which have been partly characterized by the applicants already, will be further scrutinized for potential therapeutic interventions (WP2). 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 (WP3). 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.
Network	ERA-CVD
Call	Joint Transnational Call for Proposals 2017: Mechanisms of early atherosclerosis and/or plaque instability in Coronary Artery Disease

Project partner

Number	Name	Role	Country
1	Technische Universität München	Coordinator	Germany
2	University of Tartu	Partner	Estonia
3	University Medical Center Utrecht	Partner	Netherlands