There was active discussion at the Think Tank as to whether violations of the assumption of GxE independence are commonly observed in real data. Several argued that lack of GxE independence may be rare in practice and, therefore, power gains from case-only approaches may outweigh the potential risks of increase in type I error. Support for this has been shown empirically in a GEWIS with body mass index as exposure and diabetes as the outcome [Cornelis, et al. 2012]. However, there are several plausible scenarios where one would expect G/E association in a population [Weinberg, et al. 2011]. Participants noted consideration of the violation of GxE independence assumption should be informed by previous data, experience and study characteristics. A recent empirical example in esophageal cancer demonstrates advantages and disadvantages of the case-only test compared to other methods [Wu, et al. 2013]. Determination of whether case-only analyses are appropriate will depend on the study population, exposure and disease.
