Trial reportPLoS genetics2008
A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction.
Trial report in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 13 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
174 citing papers in PubMed, 13 syntheses or guidelines pooled it, 271 citations in OpenAlex.
- Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.Nature communications · 2020Pooled 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
- 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
- Quantitative assessment of the influence of common variations (rs8034191 and rs1051730) at 15q25 and lung cancer risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.Genetic epidemiology · 2013Pooled it
- CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.Addiction (Abingdon, England) · 2012Pooled it
- Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.Archives of general psychiatry · 2012Pooled it
- Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.Genetic epidemiology · 2012Pooled 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
- Association of CHRNA4 polymorphisms with smoking behavior in two populations.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2011Pooled it
- Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.PLoS genetics · 2010Pooled it
- Meta-analysis of 15 genome-wide linkage scans of smoking behavior.Biological psychiatry · 2010Pooled it
- Light and intermittent cigarette smokers: a review (1989-2009).Psychopharmacology · 2009Pooled it
- Smoking cessation and the risk of diabetes mellitus and impaired fasting glucose: three-year outcomes after a quit attempt.PloS one · 2014Trial
- Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.Pharmacogenetics and genomics · 2013Trial
- Varenicline for smoking cessation: nausea severity and variation in nicotinic receptor genes.The pharmacogenomics journal · 2012Trial
- Trial
- Dopamine genes and nicotine dependence in treatment-seeking and community smokers.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2009Trial
- Genetic liability to meniscus degeneration and its comorbidity patterns: a phenome-wide association study in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
People who begin daily smoking at an early age are at greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic variants and nicotine dependence assessed in adulthood will be stronger among smokers who began daily nicotine exposure during adolescence. We compared nicotine addiction-measured by the Fagerstrom Test of Nicotine Dependence-in three cohorts of long-term smokers recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene approach with the neuronal nAChR subunit genes. This SNP panel included common coding variants and haplotypes detected in eight alpha and three beta nAChR subunit genes found in European American populations. In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity (p = 2.0x10(-5); odds ratio = 1.82; 95% confidence interval 1.39-2.39) in subjects who began daily smoking at or before the age of 16, an exposure period that results in a more severe form of adult nicotine dependence. A substantial shift in susceptibility versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%) was observed in the group that began smoking by age 16. This genetic effect was not observed in subjects who began daily nicotine use after the age of 16. These results establish a strong mechanistic link among early nicotine exposure, common CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent populations of European origins. The identification of an age-dependent susceptibility haplotype reinforces the importance of preventing early exposure to tobacco through public health policies.
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What OpenQuestion holds
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.