Objectives:

ENGAGE has, as its central objective, the translation of the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large-scale genetic and phenotypic data already available from a substantial number of large and well-characterised European (and other) sample sets of various types. The initial focus will be an integrated analysis of >80,000 genomewide association scans available to the consortium, thereby identifying the large number of novel disease-susceptibility variants undetectable in individual studies. Early studies will concentrate on metabolic and cardiovascular phenotypes, with subsequent expansion to apply the methods developed and lessons learned in other disease areas. The ENGAGE framework has been designed to be adaptable to advances that enable global analyses of other sources of genomic variation such as structural and epigenetic variants, and to broadening of the phenotypic spectrum (to genomic endophenotypes in particular). The clinical and public health relevance of the novel disease- and trait-susceptibility variants we identify will be evaluated using the breadth and diversity of ENGAGE cohorts (DNAs and serum/plasma samples from over 600,000 individuals). The final step will be to effect responsible clinical translation of our major findings. As well as advances in the understanding of disease pathogenesis which may underpin novel therapeutic advances, we expect to provide clear proof-of-principle that genetic and genomic discoveries can be translated into diagnostic indicators for common diseases with the capacity to stratify risk, monitor disease progression and predict and monitor therapeutic response. ENGAGE has assembled the best researchers, clinical samples and statistical and technical expertise in Europe to realise these goals.  

The overall objectives of ENGAGE are:

• To develop an enhanced supranational framework for research into genetic and genomic epidemiology that assembles the best researchers, the best sample and data sets in areas of primary focus (cardiovascular, metabolic, behavioural), the best ethical guidance and the best analytical and translational platforms;
• To accelerate discovery of disease-susceptibility genes through integrated analyses using multiple large-scale data sets and a range of experimental designs, thereby identifying novel aetiological pathways (with potential for pharmaceutical exploitation) and novel susceptibility variants and biomarkers (with potential as diagnostics as well as in guiding therapy development);
• To translate these findings into the clinical arena;
• To explore key methodological questions relevant to European research in this area (including for example, the consequences of ethnic and environmental heterogeneity for gene discovery efforts and the allelic architecture of common disease);
• To develop novel technological and statistical approaches for the study of human disease;
• To disseminate research outputs to both the scientific and non-specialist audience
• To contribute to international efforts in large population cohorts as exemplified by our very close contacts with the P3G effort (Public Population Projects in Genomics).