Systems medicine of myocardial infarction and stroke

Atherosclerosis is a leading cause of death in Europe. Until now, prevention and therapy of its most disabling sequelae, i.e. coronary artery disease (CAD) and stroke, aim at ameliorating traditional risk factors. Recently, over 50 chromosomal loci as well as novel lifestyle factors have been identified affecting CAD or stroke risk. Surprisingly, only a few of these disease markers mediate their effects via traditional risk factors. Thus, current treatment does not address all principle disease mechanisms. Future efforts should be directed at a multi-scale, patient-centered approach applying OMICs technologies including methylomics, transcriptomics, and metabolomics for quantifying the downstream impact of both genetic and life-style mediated risks. e:Athero-MED will use computational and mathematical modeling approaches to move beyond current state-of-the-art towards a holistic understanding of mechanisms and treatment options for CAD and stroke. The consortium brings together major national and international resources (e.g. prospective epidemiological and clinical samples with detailed OMICs data) and scientists from a wide spectrum of disciplines (e.g. clinicians, geneticists, epidemiologists, systems biologists, bioinformaticians, mathematicians). We intend i) to create an innovative platform for harmonizing complex data, ii) to identify itermediate phenotypes leading to disease, and iii) to utilize these insights towards the implementation of personalized prevention and treatment strategies. Specifically, we propose interrelated work packages that aim at I.) identifying disease causing gene-gene and gene-environment interactions and their implementation in prediction tools, II.) unraveling integral functional pathways of atherosclerosis, III.) investigating such pathways in experimental models of atherosclerosis, and IV.) creating IT solutions for integrating data from heterogeneous sources and for transferring newly developed algorithms and tools back into the clinic.

Subprojects in e:AtheroSysMed:

SP 1   Identification of risk alelles and risk profiles

SP 2   Multi-scale OMICs analysis for novel pathways of coronary artery disease and ischemic stroke

SP 3   Identification of disease-associated gene regulatory networks

SP 4   SNP-mediated miRNA (dys)regulation in atherosclerosis

SP 5   PWAS for identification of functional SNPs and key molecules in arterial injury

SP 6   Integration and harmonization of data, translation of results