Objective By taking advantage of great experience in genetic and cardiovascular epidemiology and some of the largest cohorts in the world including 60 000 unique individuals, the applicant aims at (1) improving CVD risk prediction and (2) identifying mechanisms causally related to CVD development in order to provide novel targets for drug discovery and targeted life style interventions for use in primary prevention.In SUBPROJECT 1 we aim at identifying disease causing alleles of loci implicated in CVD by Genome Wide Association Studies (GWAS) and to identify rare alleles with large impact on human CVD. We thus perform whole exome and targeted sequencing in early CVD cases and healthy controls and evaluate all identified variants by relating them to incident CVD in 60.000 individuals. Further, we will create a score of all validated CVD gene variants and test whether such a score improves clinical risk assessment over and above traditional risk factors.In SUBPROJECT 2 we test whether the plasma metabolome- a phenotype representing the product of dietary intake and inherent (e.g. genetic) metabolism- differs between incident CVD cases and controls and between individuals with high and low CVD genetic risk. We further test whether a life style intervention differentially alters the plasma metabolome between individuals with high and low CVD genetic risk. Finally, we will elucidate the mechanisms underlying CVD genetic associations by testing whether myocardial expression of such genes are affected by experimental myocardial infarction (MI) and whether heart function, MI size and the plasma metabolome are affected by adenoviral myocardial CVD gene transfer in rats.In SUBPROJECT 3 we test whether glucose metabolism and CVD risk factors can be ameliorated by suppressing vasopressin (VP) by increased water intake in humans. Finally, we test which of the 3 VP receptors is responsible for adverse glucometabolic VP effects in rats by specific VP receptor pharmacological studies. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health scienceshealth sciencespublic healthepidemiologymedical and health sciencesclinical medicinecardiologycardiovascular diseasesnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution LUNDS UNIVERSITET EU contribution € 1 350 000,00 Address Paradisgatan 5c 22100 Lund Sweden See on map Region Södra Sverige Sydsverige Skåne län Activity type Higher or Secondary Education Establishments Administrative Contact Lennart Råstam (Prof.) Principal investigator Olle Sten Melander (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all LUNDS UNIVERSITET Sweden EU contribution € 1 350 000,00 Address Paradisgatan 5c 22100 Lund See on map Region Södra Sverige Sydsverige Skåne län Activity type Higher or Secondary Education Establishments Administrative Contact Lennart Råstam (Prof.) Principal investigator Olle Sten Melander (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France EU contribution € 150 000,00 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Sylviane Inocencio (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
