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The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

ABSTRACT: Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample (p = 0.037). These findings suggest that (1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and (2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs.

SUBMITTER: Derringer J

PROVIDER: S-EPMC3416038 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

Derringer Jaime J Krueger Robert F RF Dick Danielle M DM Aliev Fazil F Grucza Richard A RA Saccone Scott S Agrawal Arpana A Edenberg Howard J HJ Goate Alison M AM Hesselbrock Victor M VM Kramer John R JR Lin Peng P Neuman Rosalind J RJ Nurnberger John I JI Rice John P JP Tischfield Jay A JA Bierut Laura J LJ

Behavior genetics 20120223 4

Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial ...[more]

PMID: 22358648

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Project description:BackgroundWaterpipe nicotine dependence and its association with depressive symptoms and dual usage among adolescents are currently not examined in the literature. Adolescents are a vulnerable population that is susceptible to depression and initiation of tobacco use. We aim, in this novel study, to assess the association between depressive symptoms and waterpipe nicotine dependence among adolescents in Jordan, evaluate the association between waterpipe smoking status (waterpipe smoker vs. dual user) and waterpipe nicotine dependence, and assess the internal validity of the Waterpipe Nicotine Dependence Scale (WNDS).MethodA cross-sectional study among adolescents of grade 9th to 12th in Jordan was conducted through multistage cluster random sampling. The self-reported Arabic Youth Tobacco Use Composite Measure Questionnaire (YTUCM) was used to collect the surveys that include demographic information, smoking status, and the WNDS to assess waterpipe nicotine dependence and depressive symptoms. Multiple linear regression and the t-test were used to analyze the data. Findings. One thousand three hundred and three surveys were collected, of which 1082 were included in the study (443 males and 639 females). 64.9% of the sample were nontobacco users, while 20.1% were waterpipe- (WTP-) only smokers, 11.4% were dual users, and 3.7% were cigarettes-only users. After adjusting for weights, 66.6% were nonsmokers, 19.2% were WTP-only smokers, 10.2% were dual users, and 3.9% were cigarettes-only smokers. Using multiple linear regression, depressive symptoms were significantly associated with WTP nicotine dependence (β 0.618), upon adjusting for confounders. Furthermore, dual users were associated with higher WTP nicotine dependence (β 12.034) compared to WTP-only smokers after adjusting for confounders. Cronbach's alpha for the WNDS was 0.955.ConclusionsOur study shows that there is a statistically significant association between depressive symptoms and WTP nicotine dependence and higher dependence among dual users compared to WTP-only smokers. The WNDS can be a useful tool to assess WTP nicotine dependence with high internal consistency. However, a longitudinal study is needed to further understand the association and temporality between the depressive symptoms and WTP nicotine dependence. Additionally, research is needed to shorten the WNDS while maintaining high internal consistency and assess the external validity of the WNDS and the short- and long-term consequences of dual usage.

Project description:BACKGROUND:Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES:To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. SEARCH METHODS:This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. SELECTION CRITERIA:We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. DATA COLLECTION AND ANALYSIS:We used standard methodological procedures expected by Cochrane. MAIN RESULTS:We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants and placebo (RD 0.00, 95% CI -0.01 to 0.01; RD 0.00, 95% CI -0.02 to 0.01, respectively). When we included the type of drug as a moderating variable, the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dexamphetamine than with placebo. Psychostimulants also appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone-maintained, dual heroin-cocaine addicts. Retention to treatment was low, though, so our results may be compromised by attrition bias. We found no evidence of publication bias. AUTHORS' CONCLUSIONS:This review found mixed results. Psychostimulants improved cocaine abstinence compared to placebo in some analyses but did not improve treatment retention. Since treatment dropout was high, we cannot rule out the possibility that these results were influenced by attrition bias. Existing evidence does not clearly demonstrate the efficacy of any pharmacological treatment for cocaine dependence, but substitution treatment with psychostimulants appears promising and deserves further investigation.

Dataset Information

The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

Publications

The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

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