ArticleBiological psychiatry2008
A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.
Article in Biological psychiatry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 4 of them syntheses that pooled it.
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Who cites it
98 citing papers in PubMed, 4 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review.Psychopharmacology · 2024Pooled it
- Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.Behavior genetics · 2016Pooled it
- Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans.Alcoholism, clinical and experimental research · 2015Pooled it
- Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2011Pooled it
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- Linking altered neuronal and synaptic properties to nicotinic receptor Alpha5 subunit gene dysfunction: a translational investigation in rat mPFC and human cortical layer 6.Translational psychiatry · 2025Article
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
- Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.Translational psychiatry · 2024Article
- Smoking-Related Increases in Alcohol Outcomes and Preliminary Evidence for the Protective Effect of a Functional Nicotine Receptor Gene (CHRNA5) Variant on Alcohol Consumption in Individuals Without Alcohol Use Disorder.The international journal of neuropsychopharmacology · 2024Article
- Investigating CHRNA5, CHRNA3, and CHRNB4 variants in the genetic landscape of substance use disorder in Jordan.BMC psychiatry · 2024Article
- Generalized genetic liability to substance use disorders.The Journal of clinical investigation · 2024Review
- Analogs of α-conotoxin PnIC selectively inhibit α7β2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Genotype-by-diagnosis interaction influences self-control in human cocaine addiction.Translational psychiatry · 2023Article
- Molecular genetics of cocaine use disorders in humans.Molecular psychiatry · 2022Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Addiction-related neuroadaptations following chronic nicotine exposure.Journal of neurochemistry · 2021Review
- Mechanisms of Nicotine Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms.Neuropharmacology · 2021Review
- Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals.Frontiers in neuroscience · 2021Review
- Association of CHRNA5 Gene Variants with Crack Cocaine Addiction.Neuromolecular medicine · 2020Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 9 institutions in 1 country.
Funding
Abstract
backgroundA nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence.
methodsGenetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA).
resultsIn the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD.
conclusionsThe minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.