The current enthusiasm for studying genetic associations with disease, recently enhanced by the advent of GWA studies, has tended to overshadow the important role of environmental factors and G×E interactions. While these are much more difficult to study than purely genetic associations, requiring careful collection of exposure data and rigorous study designs, standard epidemiologic designs can be used and several recently developed variants of them can enhance power. Nevertheless, large consortia will likely be needed to fully explore G×E interactions, requiring attention to these principles and harmonization across studies. The use of powerful pathway-based methods that leverage external biological knowledge can further enhance power and insight.
