This problem of contingency is also important, but sometimes ignored, in molecular genetic studies of SUDs. An appropriate control subject for a genetic study of drug dependence should have used the drug but not developed dependence. Without exposure, their specific genetic risk to dependence is unknown. However, rarely do we know how much exposure is needed to express the genetic potential for SUD. Is one cigarette enough, or one snort of cocaine? Getting a group of subjects exposed to a psychoactive drug without progression to SUD is not difficult for commonly used substances like nicotine and alcohol. It is more difficult for the ‘harder’ drugs, where exposure is rarer. If unexposed subjects are used as controls for such studies, then any differences in marker frequency factors between the SUD and control groups reflects some mixture of genetic effects on both initiation and dependence given initiation.
