We are the coordinating centre managing this large international study which started in Jan 2005. There are 7 other participants including twin/family research centres in Italy, Sweden, The Netherlands, Finland and Spain. Thrombotic stroke is a disabling condition - affecting an estimated 650,000 Europeans annually, with considerable mortality and costing over €30 billion per year. Genetic factors account for a substantial component of the incidence and mortality of stroke. There is little effective therapy. EuroClot aims to identify and validate potentially therapeutically useful genes associated with thrombotic stroke using a novel approach. Stroke is a complex end-point disease involving the interaction of many pathologic processes, such as vessel wall atheroma, hypertension, platelet function & coagulation. EuroClot focuses on uncovering the genes that control the end-stage of the coagulation process that leads directly to the production of the thrombus (clot) that causes vascular obstruction and tissue death. Clinical studies indicate that alterations in fibrin structure and/or function create a prothrombotic phenotype, which increases vascular risk. Twin studies have shown a substantial genetic component to levels of activation peptides and the final common pathway of thrombus (fibrin structure/function). EuroClot aims to identify the major genes involved in variations of the end-stage clotting process and investigate the role of these novel genes (and existing candidate genes) in the pathogenesis of stroke across Europe. EuroClot will study stroke intermediate phenotypes in over 3000 twins from the GenomEUtwin project involving 8 countries and 700 subjects from extended families from the GAIT2 (Spain) and EuroHead (Finland) studies. Genes will be validated in 1000 stroke cases including those from the large European prospective MORGAM study. Cross-European differences in allelic frequencies will be examined along with their relative impacts. Phenotyping will be standardised and harmonised and a European database established. Close links with European SMEs will ensure that all findings from EuroClot are maximally exploited to develop future novel diagnostics and therapeutic targets.
