Association of candidate genes with antisocial drug dependence in adolescents

Abstract

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 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.

Behavioral genetics in antisocial spectrum disorders and psychopathy: A review of the recent literature

“…Corley and colleagues used the phenotype of antisocial drug dependence occurring in a clinical sample and conducted analyses of 1500 snps across 50 candidate genes and found significant associations with opioid receptor mu 1 (OPRM1) and cholinergic receptor nicotinic acid 2 (CHRNA2), but not with 5HTTLPR, MAOA, or any of the other traditional sites of interest (Corley et al, 2008). Dick and colleagues also reported on a novel candidate gene from COGA for the phenotype of externalizing behavior, muscarinic acetylcholine receptor M2 (CHRM2) gene (Dick et al, 2008).…”

“…Two recent review articles focused on the genetic underpinnings of aggressive behavior (Craig & Halton, 2009;) and one article provided a review of candidate gene studies in antisocial drug dependence in adolescents (Corley et al, 2008), but none of the recent review articles located include information on the specific phenotype of psychopathy as we shall define it in this article. This article then extends upon the existing literature by presenting detailed information from recent studies purporting to examine the genetic underpinnings of antisocial spectrum disorders generally and psychopathy specifically.…”

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

“…122 The CHRNA2 3 0 UTR SNP, rs2280376, was nominally associated with antisocial drug dependence during adolescence, in a sample of 231 young Caucasian American males in treatment for drug dependence and delinquency versus matched community controls. 123 Analyzing 1500 SNPs distributed across 50 candidate genes, rs2280376 emerged with a P-value of 0.002 after permutation. Another intronic CHRNA2 SNP, rs2565065, was nominally associated with smoking cessation, in a clinical trial of bupropion versus placebo for smoking cessation in an EA sample, using Bayesian analysis of a panel of 59 SNPs in 11 candidate genes.…”

The Ethics of a Genetic Screening Study for Antisocial Personality Disorder With Mesoamericans

“…Corley et al (2008) analyzed single nucleotide polymorphisms in a sample of adolescents with antisocial behavior and drug dependence. They reported significant gene-based associations for two genes, CHRNA2 and OPRMI, compared with controls, with an OR of 1.60 (95% CI, 1.19 to 2.15); p = 0.002 and an OR of 1.47 (95% CI, 1.11 to 1.36); p = 0.006, respectively (Corley et al, 2008).…”

“…Corley et al (2008) analyzed single nucleotide polymorphisms in a sample of adolescents with antisocial behavior and drug dependence. They reported significant gene-based associations for two genes, CHRNA2 and OPRMI, compared with controls, with an OR of 1.60 (95% CI, 1.19 to 2.15); p = 0.002 and an OR of 1.47 (95% CI, 1.11 to 1.36); p = 0.006, respectively (Corley et al, 2008). Rhee and Waldman (2002) also found a genetic connection on a dual diagnosis of substance abuse and conduct disorder symptoms, showing evidence for linkage to 9q34 chromosomal region when both vulnerability to drug dependency and conduct disorder symptoms were considered.…”