Skip to main content

INTEGRATION OF GENOMICS AND CARDIOMETABOLIC PLASMA BIOMARKERS FOR IMPROVED PREDICTION AND PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE

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."

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy
  • /medical and health sciences/clinical medicine/cardiology/cardiovascular diseases

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

MAX IV Laboratory, Lund University
Address
Paradisgatan 5C
22100 Lund
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 350 000
Principal investigator
Olle Sten Melander (Prof.)
Administrative Contact
Lennart Råstam (Prof.)

Beneficiaries (2)

MAX IV Laboratory, Lund University
Sweden
EU contribution
€ 1 350 000
Address
Paradisgatan 5C
22100 Lund
Activity type
Higher or Secondary Education Establishments
Principal investigator
Olle Sten Melander (Prof.)
Administrative Contact
Lennart Råstam (Prof.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 150 000
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Sylviane Inocencio (Dr.)