Like other complex diseases with moderate heritability, substance use disorders are likely to be influenced by numerous common polymorphisms, each with only a small to moderate influence on the overall liability to the disorder (Orr et al. 2008). However, it is clear that there are also numerous environmental contributions to liability. Distinct genetic pathways may influence biological responses to specific environmental risk factors. Put simply, any given polymorphism may be important in some risk environments but not in others. It logically follows that specification of key environmental variables may aid in identifying genes that are otherwise masked under heterogeneity of the risk environment.
