Association of candidate genes with antisocial drug dependence in adolescents.

The Colorado Center For Antisocial Drug Dependence (CADD) is using several research designs and strategies in its study of the genetic basis for antisocial drug dependence in adolescents. This study reports single nucleotide polymorphism (SNP) association results from a targeted gene assay (SNP chip) of 231 primarily Caucasian male probands in treatment with antisocial drug dependence and a matched set of community controls. The SNP chip was designed to assay 1500 SNPs distributed across 50 candidate genes that have had associations with substance use disorders and conduct disorder. There was an average gene-wide inter-SNP interval of 3000 base pairs. After eliminating SNPs with poor signals and low minor allele frequencies, 60 nominally significant associations were found among the remaining 1073 SNPs in 18 of 49 candidate genes. Although none of the SNPs achieved genome-wide association significance levels (defined as p<.000001), two genes probed with multiple SNPs (OPRM1 and CHRNA2) emerged as plausible candidates for a role in antisocial drug dependence after gene-based permutation tests. The custom-designed SNP chip served as an effective and flexible platform for rapid interrogation of a large number of plausible candidate genes.