Moreover, in the classic twin design, and in sibling designs more generally, GXE interactions are confounded with additive genetic effects (in the case of genes*shared environment) and with unique environmental effects (in the case of genes*unique environment) (Eaves, 1977; Heath and Nelson, 2002). However, extended twin-family designs that control for genetic background in parents while examining differences in rearing conditions can elucidate where some GXE interactions might occur. Specifically, in one study using this approach, the absence of paternal AUD (a protective environmental factor) reduced the impact of high genetic risk for the development of an AUD in the offspring of (dependence-discordant) twins (Jacob, Waterman, Heath, True, Bucholz, Haber, et al., 2003) although similar findings were not found in another study employing a similar design (Slutske et al., 2008). Thus, perhaps the “biggest news” to come from adoption designs and children-of-twins designs is that the presumed environmental effect of living with an alcohol parent, per se, is not an important risk factor for alcohol dependence if genetic factors are adequately controlled.
