Gene Environment Association Studies Consortium (GENEVA)

5 February 2010

Genome-wide association studies (GWAS) have identified over 2,000 genetic variants associated with a range of common diseases such as diabetes and various cancers, with only a few hundred variants being convincingly replicated. Finding many common variants with a weak effect on disease risk is consistent with the common disease-common variant hypothesis and thus far only account for a small proportion of the inherited risk.

It has recently been proposed that rare variants may show much stronger effect sizes and could provide direct information about disease causation or risk (see previous news). However, it is also plausible that because nearly all GWAS thus far have concentrated on detecting and characterising main effects for genetic risk, the potential role of environmental factors modifying genetic risk has not been greatly explored, and that some of the ‘missing’ inherited risk may actually be explained by this.

Following the consortia-based approach used in many GWAS, the GENE enVironment Association studies (GENEVA) consortium was set up in 2006 by a National Institute of Health program (GEI), to accelerate the understanding of genetic and environmental contributions to health and disease by providing the support for establishing a global study management, a coordinating centre, and two genotyping centres.

A paper in the journal Genetic Epidemiology describes the GENEVA consortium, providing the aims and organisational structure as well as discussing the potential contributions from this consortium [Cornelis et al. (2010) Genet Epidemiol doi:10.1002/gepi.20492]. The aims of the GENEVA consortium are to:

1)       Identify genetic variants associated with complex diseases and traits in initial genome-wide discovery studies;

2)       Identify variations in gene-trait associations related to environmental exposures; and

3)       Ensure the rapid sharing of data to the general scientific community.

This consortium brings together 14 predominantly case-control studies with phenotypic and environmental exposure data and include people of European descent, as well as a significant number of African Americans, Hispanics and Asians. Common genotyping centres allow the use of a standardised protocol and quality control resulting in high quality genotyping data. The coordinating centre will act as a data repository as well as dealing with the logistics and administration. Although individual study investigators conduct statistical analyses, the protocols are harmonised to allow easy cross-study integration and GWAS meta-analyses.

The consortium hopes to accelerate the identification of variants involved in complex disease including via environmental interactions, allowing enhanced understanding of disease aetiology.

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