ArticleHuman molecular genetics2009
Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 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.
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Who cites it
121 citing papers in PubMed, 9 syntheses or guidelines pooled it, 185 citations in OpenAlex.
- Pooled it
- Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.Molecular psychiatry · 2020Pooled it
- Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.Molecular psychiatry · 2018Pooled 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
- Association between two CHRNA3 variants and susceptibility of lung cancer: a meta-analysis.Scientific reports · 2016Pooled 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
- Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis.Respiratory research · 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 and imputation refines the association of 15q25 with smoking quantity.Nature genetics · 2010Pooled it
- Trial
- Smoking exposure alters splicing of the nicotinic acetylcholine receptor subunit CHRNA5.Human genomics · 2026Article
- 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
- Investigating CHRNA5, CHRNA3, and CHRNB4 variants in the genetic landscape of substance use disorder in Jordan.BMC psychiatry · 2024Article
- Article
- The rs16969968 Tobacco Smoking-Related Single-Nucleotide Variant Is Associated with Clinical Markers in Patients with Severe COVID-19.International journal of molecular sciences · 2023Article
- Mutation of the α5 nicotinic acetylcholine receptor subunit increases ethanol and nicotine consumption in adolescence and impacts adult drug consumption.Neuropharmacology · 2022Article
- Article
- Comparative Assessment of Outcomes in Drug Treatment for Smoking Cessation and Role of Genetic Polymorphisms of Human Nicotinic Acetylcholine Receptor Subunits.Frontiers in genetics · 2022Article
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Genetic Variants Associated with Chronic Obstructive Pulmonary Disease Risk: Cumulative Epidemiological Evidence from Meta-Analyses and Genome-Wide Association Studies.Canadian respiratory journal · 2022Review
61 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
23 authors at 4 institutions in 1 country.
Funding
Abstract
Nicotine dependence risk and lung cancer risk are associated with variants in a region of chromosome 15 encompassing genes encoding the nicotinic receptor subunits CHRNA5, CHRNA3 and CHRNB4. To identify potential biological mechanisms that underlie this risk, we tested for cis-acting eQTLs for CHRNA5, CHRNA3 and CHRNB4 in human brain. Using gene expression and disease association studies, we provide evidence that both nicotine-dependence risk and lung cancer risk are influenced by functional variation in CHRNA5. We demonstrated that the risk allele of rs16969968 primarily occurs on the low mRNA expression allele of CHRNA5. The non-risk allele at rs16969968 occurs on both high and low expression alleles tagged by rs588765 within CHRNA5. When the non-risk allele occurs on the background of low mRNA expression of CHRNA5, the risk for nicotine dependence and lung cancer is significantly lower compared to those with the higher mRNA expression. Together, these variants identify three levels of risk associated with CHRNA5. We conclude that there are at least two distinct mechanisms conferring risk for nicotine dependence and lung cancer: altered receptor function caused by a D398N amino acid variant in CHRNA5 (rs16969968) and variability in CHRNA5 mRNA expression.
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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.