ArticleThe American journal of psychiatry2008
Variants in nicotinic receptors and risk for nicotine dependence.
Article in The American journal of psychiatry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 407 papers, 9 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
407 citing papers in PubMed, 9 syntheses or guidelines pooled it, 638 citations in OpenAlex.
- Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.Nature communications · 2026Pooled it
- Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.Drug and alcohol dependence · 2024Pooled it
- The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Pooled it
- Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease.Frontiers in oncology · 2022Pooled it
- Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Pooled it
- Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.The Cochrane database of systematic reviews · 2017Pooled it
- Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.EBioMedicine · 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
- CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.Journal of the National Cancer Institute · 2015Pooled it
- Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo-Controlled Trial.Clinical pharmacology and therapeutics · 2020Trial
- Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Trial
- Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.Drug and alcohol dependence · 2015Trial
- Genes associated with alcohol outcomes show enrichment of effects with broad externalizing and impulsivity phenotypes in an independent sample.Journal of studies on alcohol and drugs · 2015Trial
- Smoking exposure alters splicing of the nicotinic acetylcholine receptor subunit CHRNA5.Human genomics · 2026Article
- Identification and molecular functional analysis of genes associated with addiction using integrated genetic web-based programs and databases.Frontiers in genetics · 2026Article
- Nicotine: evolution, dependence, and the path to total quit: redefining cessation in a changing nicotine landscape.Frontiers in public health · 2026Review
- Ionotropic Glutamate Receptor Function in Interpeduncular Nucleus Is Modulated by Nicotine Exposure.eNeuro · 2025Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- CHRNA5-A3-B4, CYP2A6, and DBH Genetic Associations With Smoking Cessation Throughout Adulthood Within Two Longitudinal Studies of Women.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Article
347 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveA recent study provisionally identified numerous genetic variants as risk factors for the transition from smoking to the development of nicotine dependence, including an amino acid change in the alpha5 nicotinic cholinergic receptor (CHRNA5). The purpose of this study was to replicate these findings in an independent data set and more thoroughly investigate the role of genetic variation in the cluster of physically linked nicotinic receptors, CHRNA5-CHRNA3-CHRNB4, and the risk of smoking.
methodIndividuals from 219 European American families (N=2,284) were genotyped across this gene cluster to test the genetic association with smoking. The frequency of the amino acid variant (rs16969968) was studied in 995 individuals from diverse ethnic populations. In vitro studies were performed to directly test whether the amino acid variant in the CHRNA5 influences receptor function.
resultsA genetic variant marking an amino acid change showed association with the smoking phenotype (p=0.007). This variant is within a highly conserved region across nonhuman species, but its frequency varied across human populations (0% in African populations to 37% in European populations). Furthermore, functional studies demonstrated that the risk allele decreased response to a nicotine agonist. A second independent finding was seen at rs578776 (p=0.003), and the functional significance of this association remains unknown.
conclusionsThis study confirms that at least two independent variants in this nicotinic receptor gene cluster contribute to the development of habitual smoking in some populations, and it underscores the importance of multiple genetic variants contributing to the development of common diseases in various populations.
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Registered trials
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.