Another strategy that has been used to identify genes involved in adolescent substance dependence is to initially search for genetic variants associated with adult substance dependence, and then to study the risk associated with these variants in adolescent samples. One example of this strategy in use is the identification of the gene GABRA2, first found in association with alcohol dependence,48,60 and subsequently with illicit drug dependence, antisocial personality disorder, and conduct disorder, suggesting that this gene may be involved in addictions through general externalizing pathways.61 In 2006, Dick and colleagues39 extended the work on GABRA2 by using children and adolescents recruited from alcohol-dependent COGA families and control families obtained from community sources. Results suggested that individuals carrying at least 1 A allele of the SNP rs279871, which was significantly overtransmitted to alcohol-dependent subjects in the adult COGA sample, were twice as likely to meet the 3-symptom threshold of DSM-III-R conduct disorder. This effect has subsequently been replicated in an independent sample.62 These findings suggest that this gene may be involved in addictions through general externalizing pathways that manifest first as
