Following from quantitative genetic theory, if the association between parental substance dependence and offspring substance involvement results from rearing environment, offspring of affected parents should demonstrate greater risk, compared with unaffected parents (Group 1>Groups 2–4). If the association results from genes shared between parents and their children, i.e., genetic transmission, offspring at high genetic risk should exhibit earlier involvement than offspring at intermediate genetic risk regardless of environmental risk (Groups 1 and 2>Group 3). A pattern consistent with gene-environment interaction (GxE) is evident if offspring reared by an alcoholic or drug dependent parent exhibit greater risk, compared to offspring of unaffected parents, with offspring of an unaffected parent whose cotwin is also unaffected at lowest risk (Group 1>Groups 2–3>Group 4).
