Atherogenomics

We aim to further identify and functionally characterize genomic sequence variation associated with clinical manifestations of atherosclerosis. Within the timeframe of the NGFNplus program, this joint effort will provide new mechanistic insights into the molecular pathogenesis of atherosclerosis. Ultimately, the program will develop gene-based diagnostic tools and facilitate the design of novel therapeutic strategies. The Atherogenomics program builds on resources generated with funding of the recent NGFN2 program as well as other national and international sources. Particularly, the investigators characterized large patient cohorts with myocardial infarction (MI), coronary artery disease (CAD), cerebrovascular disease (CVD), peripheral arterial disease (PAD), and populations based cohorts which underwent extensive clinical and laboratory characterization for intermediate phenotypes of atherosclerosis. The initial genome-wide analysis on these samples already allowed identification of the first genes and genomic regions reproducibly associated with MI and CAD. Additional GWAs on coronary or peripheral phenotypes of atherosclerosis are completed for further in-depth interrogation. In parallel, the group performed cosegregation analyses in mice that already successfully identified novel genes involved in atherosclerosis, vascular calcification, and atheroprotection.
Thus the Atherogenomics consortium will be in the position to further study genomic variants identified in mice and man and test their clinical relevance for atherosclerosis. Particularly, we plan further exploration of GWA studies followed by validation, and globalisation of gene variants associated with atherosclerosis. Moreover, comparative genomics (mice/man) will enhance the understanding of underlying disease processes. Finally, we aim to transfer this knowledge to private enterprises for further exploitation.