ArticleHuman molecular genetics2012
Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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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Who cites it
37 citing papers in PubMed, 4 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation.Drug and alcohol dependence · 2022Pooled it
- 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
- 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
- Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.Molecular psychiatry · 2016Pooled it
- Transcriptomic Analysis of the Human Habenula in Schizophrenia.The American journal of psychiatry · 2025Article
- 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
- Human Genetics of Addiction: New Insights and Future Directions.Current psychiatry reports · 2018Review
- 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
- Expression profile of nicotinic acetylcholine receptor subunits in the brain of HIV-1 transgenic rats given chronic nicotine treatment.Journal of neurovirology · 2016Article
- Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.Behavior genetics · 2016Article
- Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions.Molecular psychiatry · 2016Review
- Crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research.Translational psychiatry · 2016Review
- Role of β4* Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Contribution of Variants in CHRNA5/A3/B4 Gene Cluster on Chromosome 15 to Tobacco Smoking: From Genetic Association to Mechanism.Molecular neurobiology · 2016Review
- 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
- Nicotine withdrawal.Current topics in behavioral neurosciences · 2015Review
- Genetics of complex traits in psychiatry.Biological psychiatry · 2015Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Genome-wide association studies have identified common variation in the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes in African American and European American nicotine-dependent smokers and smokers without symptoms of dependence. Carrier status of individuals harboring rare missense variants at conserved sites in each of these genes was then compared in cases and controls to test for an association with nicotine dependence. Missense variants at conserved residues in CHRNB4 are associated with lower risk for nicotine dependence in African Americans and European Americans (AA P = 0.0025, odds-ratio (OR) = 0.31, 95% confidence-interval (CI) = 0.31-0.72; EA P = 0.023, OR = 0.69, 95% CI = 0.50-0.95). Furthermore, these individuals were found to smoke fewer cigarettes per day than non-carriers (AA P = 6.6 × 10(-5), EA P = 0.021). Given the possibility of stochastic differences in rare allele frequencies between groups replication of this association is necessary to confirm these findings. The functional effects of the two CHRNB4 variants contributing most to this association (T375I and T91I) and a missense variant in CHRNA3 (R37H) in strong linkage disequilibrium with T91I were examined in vitro. The minor allele of each polymorphism increased cellular response to nicotine (T375I P = 0.01, T91I P = 0.02, R37H P = 0.003), but the largest effect on in vitro receptor activity was seen in the presence of both CHRNB4 T91I and CHRNA3 R37H (P = 2 × 10(-6)).
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Registered trials
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