title: Expectations and challenges stemming from genome-wide association studies.
abstract: There are considerable expectations about the ability of genome-wide association (GWA) studies to make exciting discoveries about the role of genes in common diseases. GWA studies may allow researchers to identify causal pathways that have not been unveiled before, thus opening new avenues to disease understanding, prevention and therapy. However, there are still many open challenges. One is how to analyse these studies. The problem of false positives and false negatives provides an interesting methodological stimulus to find optimal solutions. Once main genetic effects have been concretely documented, the next question is how to proceed with the investigation of gene-gene and gene-environment interactions. It is possible that what really counts is not the main effect of genes but complex interactions. Finding and interpreting such interactions is not straightforward. Finally, continuous updated integration of all evidence, from both old studies, current GWA investigations and future replication studies, and careful interpretation of the strength of the evidence are crucial to maximize transparency and lead to informative selection of the next steps of research in this field. The present Commentary is a report of an Environmental Cancer Risk, Nutrition and Individual Susceptibility network Workshop held in Venice in October 2007 and discusses some of the problems outlined above, with examples.
authors.affiliation: Department of Epidemiology and Public Health, Imperial College London, St Mary's campus, Norfolk Place, London W2 1PG, UK. p.vineis@imperial.ac.uk
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Paul
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authors.lastname: Brennan
authors.forename: Federico
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authors.lastname: Canzian
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Marylyn
authors.initials: M
authors.lastname: Ritchie
authors.forename: Ulf
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authors.lastname: Stromberg
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
authors.forename: John
authors.initials: J
authors.lastname: Thompson