Because G×E research is inherently non-experimental (even if the environmental variable is manipulated, the genetic variable cannot be), it is essential that investigators control for potential confounders in order to eliminate alternative explanations for G×E results. Unfortunately, it appears that virtually no G×E studies to date have appropriately controlled for covariates. This is not to say that previously published G×E findings are necessarily wrong; properly controlling for confounders would not have changed conclusions in some cases and may have even strengthened them in others. However, the point is that it is unknown how often G×E conclusions would have changed with properly specified models, and this is cause for concern.
