Chunk #12 — Three examples of misspecified models in the G×E literature — Kaufman et al., 2004: A gene-by-environment or an ethnicity-by-environment interaction?
Second, it is difficult and potentially misleading to interpret two-way interactions in the presence of three-way interactions. In such a model, the lower-order two-way interactions become conditional interactions, and the regression betas and p-values are interpreted as the predicted two-way interactions when the other (omitted) variable is coded as 0 (21). For example, the 5HTTLRP-by-maltreatment interaction reported by Kaufman et al. (2004) is the predicted effect of this interaction when social support is at 0. Whether “0” is meaningful (e.g., the average level of social support) or not (e.g., outside the range of the data) is essential for interpreting the lower-order interactions (the exact same issue applies to “main” effects in the context of interactions). Because the authors do not mention their final coding scheme for social support, it is not possible to know whether the reported significant two-way interaction is meaningful, although in interpreting their results above, it was assumed that the authors centered social support so that the two-way 5HTTLRP-by-maltreatment effect is the interaction predicted to occur among those at average levels of social support.
