Genetic studies of SUD need to cope with one obvious fact: genes for SUD cannot act in the absence of substance use initiation—that is, the subject starting to actually consume the substance in pharmacologically relevant amounts. Therefore, to understand SUD, we have to study the process of substance use initiation and clarify how genetic and environmental factors influence that critical first stage: the decision whether or not to consume the substance. Then, we can turn our attention to understanding the degree to which risk factors that affect substance use initiation are the same as those that affect SUD given substance use initiation. But how can we do this if we know nothing about the risk of an individual for SUD if they never initiated use of the substance?
