Confounding of GxE with rGE is of greatest concern in studies using inferred measures of genotypic variance, although certain twin models allow for the measurement and adjustment of rGE (Purcell, 2002). When genotypes and environments are both measured, as in molecular genetic GxE studies, estimates of rGE can be incorporated directly into analyses of GxE. Unfortunately, studies we reviewed inconsistently tested for rGE, and rarely considered the possible implications of interpreting GxE in the context of rGE. Studies that found significant GxE after directly adjusting for rGE provide greater confidence that the genetic factors that influence environmental exposure do not entirely account for the observed GxE findings (Tables 1 and 3), although it is still possible that unmeasured third variables account for covariation between genotypic and environmental risk.
