Genotype patterns that contribute to increased risk for or protection from developing heroin addiction

Nielsen, David A.; Ji, Fei; Yuferov, Vadim; Ho, Ann; A, Chen; Levran, Orna; Ott, Jürg; Kreek, Mary Jeanne

doi:10.1038/sj.mp.4002147

Cited by 94 publications

(88 citation statements)

References 61 publications

(60 reference statements)

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“…Polymorphisms in OPRM1 have been associated with increased craving for alcohol (van den Wildenberg et al, 2007), positive subjective responses to first use of heroin (Zhang D et al, 2006) and smoking initiation and nicotine dependence (Zhang L et al, 2006). In a recent survey of SNP differences between heroin-dependent cases and controls, a polymorphism upstream of OPRM1 was among the most significant of those located in candidate genes (Nielsen et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Association of candidate genes with antisocial drug dependence in adolescents

Corley

Zeiger

Crowley

et al. 2008

Drug and Alcohol Dependence

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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.

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Section: Discussionmentioning

confidence: 99%

Association of candidate genes with antisocial drug dependence in adolescents

Corley

Zeiger

Crowley

et al. 2008

Drug and Alcohol Dependence

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“…The TT genotype was associated with quantitative measures of substance use in African American women (108). Additional non-coding OPRM1 SNPs have been indicated in drug addiction and response to drugs, including intronic variants (109-111) and a variant in the 5′ region near the gene (112), but their function is yet unknown.…”

Section: The Genetics Of Drug Addictionsmentioning

confidence: 99%

Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

Kreek¹,

Levran²,

Reed³

et al. 2012

J. Clin. Invest.

186

121

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Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.

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“…Heroin Addiction [21] Although not formally significant, our partition test furnishes a stronger result (p = 0.0529) than any singlelocus test (0.1951).…”

Section: Response To Platinum-based Chemotherapymentioning

confidence: 95%

Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies

Ott

Liu²,

Shen³

2012

Hum Hered

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Background/Aims: We consider the situation that multiple genetic variants are underlying a heritable trait and assume that each contributes to the trait only to a small degree. The aim is to develop a statistical test for disease association of these multiple variants. Methods: We expect that p values resulting from a genome-wide case-control association analysis will fall into two classes: those reflecting true association and those occurring randomly in the interval from 0 to 1. We develop a partition test to find the set of smallest p values deviating most from the number of p values expected under randomness. Results: Power calculations demonstrate the superiority of our partition test over conventional SNP-by-SNP analyses. Applications of the partition test to six published datasets show that our test is particularly suitable when multiple SNPs appear to contribute to a trait, and furnished more significant results than a well-known procedure to estimate the false discovery rate. Conclusions: Our partition test also furnishes an estimate of the number of functional SNPs underlying disease and can be highly significant, while single-locus tests may be far from significant.

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Genotype patterns that contribute to increased risk for or protection from developing heroin addiction

Cited by 94 publications

References 61 publications

Association of candidate genes with antisocial drug dependence in adolescents

Association of candidate genes with antisocial drug dependence in adolescents

Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies

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