Thirdly, the present findings have to be viewed in the light of a number of difficulties inherent in the detection of “true” gene-environment interactions. Major issues of criticism relate to the potential for multiple testing, low statistical power, and the lack of criteria for replication. Multiple testing has long been a serious problem in genetic research. The availability of datasets which afford large numbers of subdivisions (due to different ways of defining genotype and environmental characteristics) multiplies the potential of multiple testing by offering numerous additional possibilities for data mining [43]. Another difficulty in genetic association research is that many studies lack sufficient statistical power. Since statistical tests for examining interaction effects are less powerful than tests of main effects, this problem applies particularly to studies of GxE. The power to detect an interaction depends on a number of conditions, including the sample size as well as the distribution of genotypes and environmental exposures in the sample. Given the likely small effects of any single GxE and the associated risk of false positive results, this argues for the critical need
