The ideal approach, suggested in a parallel set of simulations of G × E in twin data (Eaves 2014) is to integrate the model for genetic and environmental effects on liability with an item-response theory (IRT) model for the relationship between latent trait and test responses. If the IRT model is correctly specified, unbiased tests of the main effects may be recovered and some of the problems of misleading inference may be avoided. This approach has still to be tested fully in the candidate-gene context (though see Wray et al. 2008) but would seem to be a sine qua non for the development of a credible research program in the study of G × E.
