ArticleBiological psychiatry2011
Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence.
Article in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.Biological psychiatry · 2019Pooled it
- Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.Molecular psychiatry · 2018Pooled it
- Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Pooled it
- Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.Translational psychiatry · 2015Pooled it
- Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.Pharmacogenetics and genomics · 2013Trial
- Article
- A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans.Translational psychiatry · 2019Article
- Opioid Addiction, Genetic Susceptibility, and Medical Treatments: A Review.International journal of molecular sciences · 2019Review
- Considering Genetic Heterogeneity in the Association Analysis Finds Genes Associated With Nicotine Dependence.Frontiers in genetics · 2019Article
- The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018Review
- Informing Prevention and Intervention Policy Using Genetic Studies of Resistance.Prevention science : the official journal of the Society for Prevention Research · 2018Article
- Genome-wide meta-analysis identifies a novel susceptibility signal at CACNA2D3 for nicotine dependence.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Article
- Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2017Article
- Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2016Article
- Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.Behavior genetics · 2016Article
- CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Article
- Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.Molecular psychiatry · 2016Review
- A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.Molecular psychiatry · 2016Article
- Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use.Genes, brain, and behavior · 2016Review
- The contribution of rare and common variants in 30 genes to risk nicotine dependence.Molecular psychiatry · 2015Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundSeveral studies report association of alpha-4 nicotinic acetylcholine receptors (encoded by CHRNA4) with nicotine dependence (ND). A meta-analysis of genomewide linkage studies for ND implicated a single chromosomal region, which includes CHRNA4, as genome-wide significant.
methodsAfter establishing that common variants are unlikely to completely account for this linkage, we investigated the distribution of CHRNA4 rare variants by sequencing the coding exons and flanking intronic regions of CHRNA4 in 209 European American (EA) ND cases and 183 EA control subjects. Because most of the rare variants that we detected (and all nonsynonymous changes) were in Exon 5, we sequenced Exon 5 in an additional 1000 ND cases and 1000 non-ND comparison subjects, both of which included equal numbers of EAs and African Americans.
resultsComparison subjects had a higher frequency of rare nonsynonymous variants in the Exon 5 region (encoding the large intercellular loop of the α4 subunit; Fisher's Exact Test p = .009; association test p = .009, odds ratio = .43; weighted-sum method p = .014), indicating a protective effect against ND. Considering data from the two stages combined and only nonsynonymous variants predicted to alter protein function, the association was stronger (Fisher's Exact Test p = .005; association test p = .008, odds ratio = .29; weighted-sum method p = .005). Single-photon emission computed tomography imaging results were consistent with functionality.
conclusionsCHRNA4 functional rare variants may reduce ND risk. This is the first demonstration that rare functional variants at a candidate locus protect against substance dependence to our knowledge, suggesting a novel mechanism of substance dependence heritability that is potentially of general importance.
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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.