rs16969968
| Orientation | plus |
| Stabilized | plus |
| Geno | Mag | Summary |
|---|---|---|
| (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 |
| (G;G) | 0 | normal |
| Reference | GRCh38 38.1/141 |
| Chromosome | 15 |
| Position | 78590583 |
| Gene | CHRNA5 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs16969968 |
| dbSNP (classic) | rs16969968 |
| ClinGen | rs16969968 |
| ebi | rs16969968 |
| HLI | rs16969968 |
| Exac | rs16969968 |
| Gnomad | rs16969968 |
| Varsome | rs16969968 |
| LitVar | rs16969968 |
| Map | rs16969968 |
| PheGenI | rs16969968 |
| Biobank | rs16969968 |
| 1000 genomes | rs16969968 |
| hgdp | rs16969968 |
| ensembl | rs16969968 |
| geneview | rs16969968 |
| scholar | rs16969968 |
| rs16969968 | |
| pharmgkb | rs16969968 |
| gwascentral | rs16969968 |
| openSNP | rs16969968 |
| 23andMe | rs16969968 |
| SNPshot | rs16969968 |
| SNPdbe | rs16969968 |
| MSV3d | rs16969968 |
| GWAS Ctlg | rs16969968 |
| GMAF | 0.1749 |
| Max Magnitude | 3 |
| ? | (A;A) (A;G) (G;G) | 28 |
|---|---|---|
|
| ||
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
]
In a study 500+ individuals with cocaine dependence, the same rs16969968(A) allele was associated with a 0.67x decreased risk (p = 0.0045).[PMID 18519132]
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]
23andMe blog 23andMe considers rs1051730 equivalent
[PMID 18978134] The association between rs16969968 and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.
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 19465454] The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
| OMIM | 118505 |
| Desc | CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 5; CHRNA5 |
| Variant | |
| Related | also |
[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 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
| ClinVar | |
|---|---|
| Risk | Rs16969968(A;A) |
| Alt | Rs16969968(A;A) |
| Reference | Rs16969968(G;G) |
| Significance | Other |
| Disease | Lung cancer susceptibility 2 Smoking as a quantitative trait locus 3 |
| Variation | info |
| Gene | CHRNA5 |
| CLNDBN | Lung cancer susceptibility 2 Smoking as a quantitative trait locus 3 |
| Reversed | 0 |
| HGVS | NC_000015.9:g.78882925G>A |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000019049.3, RCV000033213.3, |
[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.
[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.
[PMID 29172281] SNP rs16969968 as a Strong Predictor of Nicotine Dependence and Lung Cancer Risk in a North Indian Population
[PMID 29573323] The interaction of the Chrna5 D398N variant with developmental nicotine exposure.
[PMID 30453884] Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence.
[PMID 32841724] Alterations in nicotinic receptor alpha5 subunit gene differentially impact early and later stages of cocaine addiction: a translational study in transgenic rats and patients.
