Final Report Summary - EUROCLOT (Genetic regulation of the end-stage clotting process that leads to thrombotic stroke)
The aim of EUROCLOT was 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 would study stroke intermediate phenotypes in over 3 000 twins from GenomEUtwin project involving 8 countries and 700 subjects from extended families from the GAIT2 (Spain) and EuroHead (Finland) studies. Genes would be validated in 1 000 stroke cases including those from the large European prospective MORGAM study. Cross-European differences in allelic frequencies would be examined along with their relative impacts. Phenotyping would be standardised and harmonised and a European database established.
Progress of the project overall has been satisfactory with all of the deliverables have been met. Gene-environment interactions were explored using linear regression of the replicated loci for variations with the major environmental factors - smoking, BMI and fasting insulin and glucose levels - and no clear significant interactions were found. This study was, however, not sufficiently powered to observe small to moderate gene-environment interactions, given the modest effect sizes of the genetic risk factors found in GWA studies and no major gene-environment interaction was detected.