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Most of the common-complex, chronic diseases, that have a high prevalence in our populations, arise through interaction between genetic, environmental and life-style factors. To understand the composite origin of these diseases, we need first to know the path from genotype to phenotype. A complex trait is phenotypically and genetically heterogeneous and thus requires a global genomic approach to understand its etiology and pathogenesis. Such a global approach has not been feasible until recently. So far, all experimental investigations dealt with "single" pieces (eg. genes) of the whole pattern: however relevant the findings, we still lack a broader and comprehensive view of a complex disease per se.

To define a comprehensive genetic epidemiological model of complex traits, we propose to apply new, but already well-established technologies of high throughput genotyping, analyzed with sophisticated statistical-mathematical modelling, to already existing cohorts of subjects with essential hypertension (EH) and intermediate phenotypes of hypertension dependent/associated Target Organ Damages (TOD).

The aim of our integrated approach is to develop an exhaustive model to disentangle the genetic bases of a complex disease using population genetic epidemiology as a methodological tool. We have chosen EH as the disease model, both because of our long-term experience in investigating the genetics of EH and because the cardiovascular complications remain the major cause of death in the EU. Its impact in terms of cost and disability are a devastating burden for patients, for their relatives and for the human potential of the EU. Designing a comprehensive genetic epidemiological model of complex traits will also help us to translate genetic findings into improved diagnostic accuracy and new strategies for early detection, prevention and eventually personalised treatment of a complex trait.

Needless to say, the ultimate goal will be to promote the quality of life of EU populations. For more information, please go to: http://www.hypergenes.eu/

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• D Cusi (Milan, I)(Lead)
• J Staessen (Leuven, B)
• K Kawecka-Jaszcz (Krakow, PL)
• A Shabo (Haifa, IS)
• E Kovic (Ljubljana, SLO)
• P Conti (Milan, I)
• Y Nikitin (Novosibirsk, RUS)
• P Vineis (London, GB)
• X Jeunemaitre (Paris, F)
• F P Cappuccio (Warwick, GB)
• N Glorioso (Sassari, I)
• M Palmieri (Catania, I)
• C Rivolta (Lausanne, CH)
• D Cohen (Evry, F)
• E Morten (Genoa, I)
• J Wang (Shanghai, PRC)
• J Filipovsky (Prague, CK)
• E Casiglia (Padua, I)
• K Narkiewicz (Gdansk, PL)

 FP7 Health Programme - grant agreement 201550, HEALTH-2007-2.1.1-2 "Molecular epidemiological studies in existing well characterised European (and/or other) population cohorts."

In progress