For GEWIS studies of SNP × E for discovery, the Think Tank participants discussed setting a threshold for genome-wide GxE significance. Thresholds in the 5×10−7 to 1×10−8 range have been an important component of the standards and success of GWAS [Chanock, et al. 2007]. Although specifics about appropriate significance thresholds for the GWAS setting are still actively debated [Panagiotou, et al. 2012; Wakefield 2012], thresholds are viewed as a pragmatic way to determining what is “established” and curtailing false positives. However, a concern was raised at the Think Tank as to whether it is too early to establish fixed thresholds for GxE, since there have not been a sufficient number of large studies with replication to empirically evaluate a threshold standard. There was additional concern that it is not clear what decision we are trying to make with a threshold. Specifically, are we using a threshold to determine when an interaction is real, or using a threshold more broadly to determine whether interactions are noteworthy and merit further follow-up? Additionally, there was concern that a statistical threshold may represent too
