The case-only method tests the association between the environmental factor and the genetic factor within cases, and has improved power over the traditional logistic regression method[Piegorsch, et al. 1994]; however, the case-only method has a large type I error if the GxE independence assumption is violated [Albert, et al. 2001]. This method loses power when the interaction odds ratio and the association between the gene and environmental exposure are in opposite directions [Mukherjee and Chatterjee 2008], and is less powerful when the disease is common.
