|(A;A)||3||higher risk for nicotine dependence, lower risk for cocaine dependence|
|(A;G)||2.5||slightly higher risk for nicotine dependence, lower risk for cocaine dependence|
Associated with smoking phenotype (p=0.007) based on association study of 2,000+ individuals, and functional studies demonstrated that the risk allele decreased response to a nicotine agonist, therefore the rs16969968(A) allele is likely to be involved in nicotine dependence.[PMID 18519524]
A study of 200 individuals replicated the association between this SNP and nicotine dependence, and also concluded that the rs16969968(A) allele was significantly associated with "enhanced pleasurable responses" to a person's first cigarette.[PMID 18783506]
rs16969968 increases susceptibility to Substance dependence, Nicotine 1.10 times for heterozygotes (AG) and 1.90 times for homozygotes (AA) [PMID 17135278]
plos Risk Factors for Age-Dependent Nicotine Addiction
[PMID 19259974] Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes.
[PMID 19706806] A Novel Polymorphism rs1329149 of CYP2E1 and a Known Polymorphism rs671 of ALDH2 of Alcohol Metabolizing Enzymes Are Associated with Colorectal Cancer in a Southwestern Chinese Population
[PMID 19465454] The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
[PMID 19706762] The CHRNA5-CHRNA3-CHRNB4 Nicotinic Receptor Subunit Gene Cluster Affects Risk for Nicotine Dependence in African-Americans and in European-Americans
[PMID 19706810] Variants Weakly Correlated with CHRNA5 D398N Polymorphism Should be Considered in Transcriptional Deregulation at the 15q25 Locus Associated with Lung Cancer Risk
[PMID 19733931] Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
[PMID 19776245] Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals
[PMID 19896728] Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25
[PMID 19132693] Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence
[PMID 20056643] A rigorous and comprehensive validation: common genetic variations and lung cancer
[PMID 19482438] Association of genes coding for the alpha-4, alpha-5, beta-2 and beta-3 subunits of nicotinic receptors with cigarette smoking and nicotine dependence
[PMID 20587604] Fine Mapping of Chromosome 15q25.1 Lung Cancer Susceptibility in African Americans
[PMID 20700147] Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 5' upstream polymorphisms
[PMID 20700436] Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
[PMID 20840187] Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence
[PMID 20871796] Interplay of Genetic Risk Factors and Parent Monitoring in Risk for Nicotine Dependence
[PMID 21229299] Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers[PMID 21418140] A CHRNA5 Allele Related to Nicotine Addiction and Schizophrenia
[PMID 21750227] Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)
[PMID 21764527] Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women
[PMID 22012472] Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with ?5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
[PMID 22046326] 'Smoking Genes': A Genetic Association Study
[PMID 21618602] Detecting genetic interactions for quantitative traits with U-statistics
[PMID 21858091] In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression
[PMID 22406075] Association of single nucleotide polymorphisms of nicotinic acetylcholine receptor subunits with cervical neoplasia
[PMID 22665477] Function of Human α3β4α5 Nicotinic Acetylcholine Receptors is Reduced by the α5(Asp398Asn) Variant
[PMID 22008662] The association of the alpha-5 subunit of the nicotinic acetylcholine receptor gene and the brain-derived neurotrophic factor gene with different aspects of smoking behavior.
[PMID 21966413] Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population
[PMID 22534784] Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure
|Disease||Lung cancer susceptibility 2 Smoking as a quantitative trait locus 3|
|CLNDBN||Lung cancer susceptibility 2 Smoking as a quantitative trait locus 3|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
[PMID 18165968] Identification of pharmacogenetic markers in smoking cessation therapy.
[PMID 18227835] Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking.
[PMID 18385676] Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
[PMID 18414406] Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence.
[PMID 18565990] Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence.
[PMID 18571741] Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research.
[PMID 18759969] In search of causal variants: refining disease association signals using cross-population contrasts.
[PMID 18780872] Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer.
[PMID 18957677] The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer.
[PMID 19005185] Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese.
[PMID 19010884] Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine.
[PMID 19029397] Nicotinic receptor gene variants influence susceptibility to heavy smoking.
[PMID 19064933] Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.
[PMID 19184766] A testable prognostic model of nicotine dependence.
[PMID 19238175] New insights into the genetics of addiction.
[PMID 19247474] Genome-wide and candidate gene association study of cigarette smoking behaviors.
[PMID 19300482] A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci.
[PMID 19330903] Gene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican-Americans.
[PMID 19390575] Lung cancer susceptibility model based on age, family history and genetic variants.
[PMID 19436041] Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes.
[PMID 19443489] Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19492010] The genetic components of alcohol and nicotine co-addiction: from genes to behavior.
[PMID 20485328] Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes.
[PMID 20529875] SPOT: a web-based tool for using biological databases to prioritize SNPs after a genome-wide association study.
[PMID 20548021] Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.
[PMID 20725741] Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity.
[PMID 20808433] Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a Korean population.
[PMID 20886544] Risk gene variants for nicotine dependence in the CHRNA5-CHRNA3-CHRNB4 cluster are associated with cognitive performance.
[PMID 21268243] Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy.
[PMID 21304900] Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
[PMID 21335511] A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.
[PMID 21385908] Association of the nicotine metabolite ratio and CHRNA5/CHRNA3 polymorphisms with smoking rate among treatment-seeking smokers.
[PMID 21430647] The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment.
[PMID 21810735] Single nucleotide polymorphisms in CHRNA5 rs16969968, CHRNA3 rs578776, and LOC123688 rs8034191 are associated with heaviness of smoking in women in Northeastern Ontario, Canada.
[PMID 21856741] Functional characterization of the alpha5(Asn398) variant associated with risk for nicotine dependence in the alpha3beta4alpha5 nicotinic receptor.
[PMID 21862624] Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC.
[PMID 21955800] The polymorphism of the CHRNA5 gene and the strength of nicotine addiction in lung cancer and COPD patients.
[PMID 22028403] A case-control study of a sex-specific association between a 15q25 variant and lung cancer risk.
[PMID 22071378] Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis.
[PMID 22102629] Dissection of the phenotypic and genotypic associations with nicotinic dependence.
[PMID 22223462] Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.
[PMID 22539395] Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.
[PMID 22544838] From Men to Mice: CHRNA5/CHRNA3, Smoking Behavior and Disease.
|qualified_impact||Insufficiently evaluated pathogenic|
|summary||Associated with early onset addiction to nicotine and with susceptibility to lung cancer.|
[PMID 23196875] Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder
[PMID 23221128] Fine-mapping of the 5p15.33, 6p22.1-p21.31 and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans
[PMID 23232035] Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans
[PMID 23443019] Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56 307 individuals from the HUNT study in Norway
[PMID 23308091] A complex interplay between personality domains, marital status and a variant in CHRNA5 on the risks of cocaine, nicotine dependences and cocaine-induced paranoia
[PMID 24296975] Nicotine consumption is regulated by a human polymorphism in dopamine neurons
[PMID 24303001] Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry
[PMID 22820273] Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by alpha3beta4alpha5 nicotinic acetylcholine receptors.
[PMID 22884254] Association of nicotine dependence susceptibility gene, CHRNA5, with Parkinson's disease age at onset: gene and smoking status interaction.
[PMID 22914670] Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population.
[PMID 23178447] Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population.
[PMID 23334941] A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity.
[PMID 23358500] Variation in the alpha 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content.
[PMID 23404318] Interpreting joint SNP analysis results: when are two distinct signals really two distinct signals?
[PMID 23454887] Role of selected genetic variants in lung cancer risk in African Americans.
[PMID 23692359] CHRNA5-A3-B4 genetic variants alter nicotine intake and interact with tobacco use to influence body weight in Alaska Native tobacco users.
[PMID 25051068] Four SNPs in the CHRNA3/5 Alpha-Neuronal Nicotinic Acetylcholine Receptor Subunit Locus Are Associated with COPD Risk Based on Meta-Analyses
[PMID 25293386] Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
[PMID 25652844] Nicotine dependence in an isolated population of Kashubians from North Poland: a population survey
[PMID 25873736] CHRNA5 Risk Variant Predicts Delayed Smoking Cessation and Earlier Lung Cancer Diagnosis-A Meta-Analysis
[PMID 25911614] Crucial role of nicotinic α5 subunit variants for Ca2+ fluxes in ventral midbrain neurons
[PMID 25950378] Effect of the rs1051730-rs16969968 variant and smoking cessation treatment: a meta-analysis
[PMID 25948103] A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans
[PMID 26142345] Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation
[PMID 26220977] A multiancestry study identifies novel genetic associations with CHRNA5 methylation in human brain and risk of nicotine dependence
[PMID 26264275] Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium
[PMID 26434895] CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer - Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects
[PMID 26538566] Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium
[PMID 27698409] Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele.
[PMID 28533558] Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.