Because of the challenges associated with gene identification efforts for multifactorial traits (traits that are influenced by multiple genes and environments) such as substance dependence, several strategies have been used to identify genes involved in addictive disorders. One approach is the candidate gene approach. This strategy involves investigation of a gene that is believed to be involved in the cause of a specific disorder for known or hypothesized biologic reasons. A classic example of the candidate gene approach is the association of genes involved in alcohol metabolism with susceptibility to alcohol dependence. Multiple alcohol-metabolism genes have been repeatedly implicated in the development of alcohol addiction and susceptibility to dependence on other drugs. These genes were initially suspected as having a role in dependence, as they are known to be involved in the metabolism of ethanol. For example, alcohol dehydrogenase 1B (ADH1B) is involved in the conversion of ethanol to acetaldehyde; acetaldehyde is toxic and its accumulation leads to an unpleasant physiologic reaction involving headache, nausea, and heart palpitations. Polymorphisms in alcohol metabolism genes that affect acetaldehyde levels can have a
