Objectives

We aim to unravel the genetic basis of thrombotic stroke leading to new diagnostics and drug targets by:

1. Identifying susceptibility loci and genes for the end stages and final common pathways of clotting, through:
   • Genome-wide linkage and analysis
   • Generating a list of candidate genes
   • Chromosome specific linkage analysis and fine mapping
   • Candidate gene analysis
2. Evaluating the importance of these genetic factors in the general European population, through
   • The comparison of candidate gene allele frequencies between European cases and controls with stroke
   • Assessing the relative contribution of these gene variants in clot formation
3. Investigating how identified genetic variants vary in influence and frequency of stroke in Northern and Southern Europe, through:
   • Candidate gene variants which will be tested for frequency differences between twin and family populations in Sweden and Finland in the North and Italy and Spain in the South.
4. Identifying genes controlling fibrin formation or activation that will become important diagnostic tests used in conjunction with other markers or genes, through:
   • Phenotypes for fibrin function
   • Candidate genes
   • Diagnostic uses
5. Enhancing the understanding of the mechanisms involved to provide potential new drug targets for the prevention of or treatment of early stroke, through:
   • Linkage analysis showing extent of likely new candidates
   • Detailed analysis of candidates potentially showing insight into new mechanisms
   • Mechanistic links between physiology and pathology evident from case-control analysis
6. Working with SMEs to exploit findings for clinical benefit, through:
   • Tests of fibrin function which will be evaluated for potential simplification and commercialisation by diagnostic SMEs
   • Discussion with diagnostic and genomic SMEs
7. Generating genotypic and phenotypic data for concordant and discordant twin pairs for future studies evaluating environmental effects on stroke pathogenesis and expression, through:
   • A Phenotype database
   • A Genotype database
   • DNA data
8. Increasing interest and reinforcing the leading role of European researchers in thrombotic stroke research, through:
   • Establishing a website showing the results of the EuroClot project with links to other relevant websites
   • Publications and press releases
   • Presentations at international meetings