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 for replication. However, differences in the measurement instruments, in assessing genotype, phenotype and environmental variables, between studies complicate to find comparable studies [44]. However, recent meta-analyses, e.g. by Karg et al. [39], have demonstrated that replication of GxE effects is actually possible, and that problems, such as low statistical power, could be overcome by using an at-risk group approach. In this line, the results reported here should be considered with caution regarding the sample size and the number of statistical tests performed. Hence, we do not exclude the possibility that the reported associations in the present study may reflect false-positive results (type 1 error), given that the discovery set is rather small and no replication or functional work is available. Also, it should be emphasized that the associations we observed are small in effect and would not hold up to stringent correction for multiple testing and thus should be regarded as preliminary.
