HuGENet™ Workshop on the Assessment of Cumulative Evidence on Genetic Associations: International Workshop held in Venice (Italy) on 9-10 November 2006

Many gene variants have been assessed in relation to a wide range of outcomes, and an increasing number of genetic factors are being investigated in relation to any one specific outcome.  For decision making, it would be valuable to integrate evidence for different genetic factors for one outcome, and for multiple outcomes in relation to a specific genetic factor. The publication of synopses of the cumulative evidence on genetics and population health in specific fields could address a gap resulting from the fact that systematic reviews and meta-analyses tend to focus only on one or a few specific gene-disease associations at a time. However, a prerequisite is to agree on widely acceptable criteria for assessing cumulative evidence.

Several assessment schemes have been proposed (1-8), but some overlap with the assessment of single studies, and the schemes differ from one another. Considerations for inferring causation from observational studies of associations between exposures and disease were proposed in the 1960s (9, 10) and have been modified for different field of epidemiological investigation (11-13). However, the relevance of these considerations to current and evolving challenges of human genome epidemiology needs to be assessed.

Following the initial meeting of the Network of Networks in October 2005 (14), a HuGENet Working Group on the Assessment of Evidence was established. This Group reviewed evidence on assessment and grading schemes from other biomedical fields, and discussed options for developing schemes specific to genetic associations. A workshop was organized in Venice on November 9-10, 2006 where a multi-disciplinary panel of around 25 experts discussed these issues. The panel discussed existing assessment schemes from other fields, experiences of developing synopses of cumulative evidence on diverse diseases, attempts to link human genome epidemiology with other biological and experimental evidence relevant to acute, infectious, and chronic diseases, the framework for causal inference, and methods for the efficient assessment of quantity and quality of cumulative evidence.

An initial set of guidelines was agreed and will be refined over the coming months. The workshop presentations will shortly be made available on the Canadian HuGENet Coordinating Centre website (http://www.hugenet.ca) . The development of a system of assessment of cumulative evidence on genetic associations and related interactions is likely to be iterative, and will be informed by further experience gained in developing synopses of cumulative evidence (15). In addition, further work is ongoing about linking these guidelines with biological and experimental evidence.

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