{{Rsnum
|rsid=16969968
|Gene=CHRNA5
|Chromosome=15
|position=78590583
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.1749
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=CHRNA5
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 15.9 | 45.1 | 38.9
| HCB | 0.0 | 5.2 | 94.8
| JPT | 0.0 | 4.4 | 95.6
| YRI | 0.0 | 0.0 | 100.0
| ASW | 1.8 | 12.3 | 86.0
| CHB | 0.0 | 5.2 | 94.8
| CHD | 0.0 | 7.3 | 92.7
| GIH | 5.9 | 30.7 | 63.4
| LWK | 0.0 | 0.9 | 99.1
| MEX | 5.2 | 34.5 | 60.3
| MKK | 0.6 | 17.3 | 82.1
| TSI | 18.6 | 43.1 | 38.2
| HapMapRevision=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|OA=1
}}

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|OA=1
}}

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|OA=1
}}

[http://blog.23andme.com/2008/08/20/snpwatch-focusing-on-a-gene-variant-that-might-help-counter-cigarette-cravings/ 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|OA=1
}}

[http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000125 plos] Risk Factors for Age-Dependent Nicotine Addiction

{{PMID Auto
|PMID=19259974
|Title=Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes.
|OA=1
}}

{{PMID Auto
|PMID=19465454
|Title=The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
}}

{{omim
|id=612052
|desc=LUNG CANCER SUSCEPTIBILITY 2; LNCR2
|rsnum=16969968
}}

{{omim
|id=118505
|desc=CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 5; CHRNA5
|rsnum=16969968
}}
{{PMID Auto
|PMID=19706806
|Title=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 Auto
|PMID=19706762
|Title=The CHRNA5-CHRNA3-CHRNB4 Nicotinic Receptor Subunit Gene Cluster Affects Risk for Nicotine Dependence in African-Americans and in European-Americans
|OA=1
}}
{{PMID Auto
|PMID=19706810
|Title=Variants Weakly Correlated with CHRNA5 D398N Polymorphism Should be Considered in Transcriptional Deregulation at the 15q25 Locus Associated with Lung Cancer Risk
}}
{{PMID Auto
|PMID=19733931
|Title=Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
}}
{{PMID Auto
|PMID=19776245
|Title=Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals
|OA=1
}}
{{PMID Auto
|PMID=19896728
|Title=Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25
|OA=1
}}

{{PharmGKB
|RSID=rs16969968
|Name_s=CHRNA5:Asp398Asn
|Gene_s=CHRNA5
|Feature=
|Evidence=PubMed ID:18618000
|Annotation=The A allele of this SNP is associated with early onset nicotine addiction, i.e., daily smoking commencing at or before age 16. Haplotype A, which is defined by the A allele of this SNP and the A allele of rs1051730, is similarly associated with early onset nicotine dependence.
|Drugs=nicotine
|Drug Classes=
|Diseases=Tobacco Use Disorder
|Curation Level=Curated
|PharmGKB Accession ID=PA162168238
}}
{{PMID Auto
|PMID=19132693
|Title=Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence
|OA=1
}}
{{PMID Auto
|PMID=20056643
|Title=A rigorous and comprehensive validation: common genetic variations and lung cancer
|OA=1
}}

{{PMID Auto
|PMID=19482438
|Title=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 Auto
|PMID=20587604
|Title=Fine Mapping of Chromosome 15q25.1 Lung Cancer Susceptibility in African Americans
|OA=1
}}
{{PMID Auto
|PMID=20700147
|Title=Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 5' upstream polymorphisms
|OA=1
}}
{{PMID Auto
|PMID=20700436
|Title=Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
|OA=1
}}
{{PMID Auto
|PMID=20840187
|Title=Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence
|OA=1
}}
{{PMID Auto
|PMID=20871796
|Title=Interplay of Genetic Risk Factors and Parent Monitoring in Risk for Nicotine Dependence
|OA=1
}}
{{PMID Auto
|PMID=21229299
|Title=Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers
|OA=1
}}

{{omim
|id=118505
|rsnum=16969968
|variant=0001
}}

{{PMID Auto
|PMID=21418140
|Title=A CHRNA5 Allele Related to Nicotine Addiction and Schizophrenia
|OA=1
}}

{{PMID Auto
|PMID=21750227
|Title=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 Auto
|PMID=21764527
|Title=Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women
|OA=1
}}

{{PMID Auto
|PMID=22012472
|Title=Childhood Adversity Increases Risk for Nicotine Dependence and Interacts with ?5 Nicotinic Acetylcholine Receptor Genotype Specifically in Males
|OA=1
}}

{{PMID Auto
|PMID=22046326
|Title='Smoking Genes': A Genetic Association Study
|OA=1
}}

{{PMID Auto
|PMID=21618602
|Title=Detecting genetic interactions for quantitative traits with U-statistics
|OA=1
}}

{{PMID Auto
|PMID=21858091
|Title=In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression
|OA=1
}}

{{PMID Auto
|PMID=22406075
|Title=Association of single nucleotide polymorphisms of nicotinic acetylcholine receptor subunits with cervical neoplasia
}}

{{PMID Auto
|PMID=22665477
|Title=Function of Human α3β4α5 Nicotinic Acetylcholine Receptors is Reduced by the α5(Asp398Asn) Variant
|OA=1
}}

{{PMID Auto
|PMID=22008662
|Title=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 Auto
|PMID=21966413
|Title=Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population
|OA=1
}}

{{PMID Auto
|PMID=22534784
|Title=Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure
|OA=1
}}

{{ClinVar
|rsid=16969968
|Reversed=0
|FwdREF=G
|FwdALT=A
|REF=G
|ALT=A
|RSPOS=78882925
|CHROM=15
|GMAF=0.1754
|dbSNPBuildID=123
|SSR=0
|SAO=1
|VP=0x05026800000015051f110100
|GENEINFO=CHRNA5:1138
|GENE_NAME=CHRNA5
|GENE_ID=1138
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000015.9:g.78882925G>A
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;PMC;S3D;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.8251; 0.1749
|CLNACC=RCV000019049.1; RCV000033213.1
|CLNDBN=Lung cancer susceptibility 2; Smoking as a quantitative trait locus 3
|CLNDSDB=MedGen; MedGen:OMIM
|CLNDSDBID=C2677571; C3150168:612052
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=118505.0001
|COMMON=1
|Disease=Lung cancer susceptibility 2; Smoking as a quantitative trait locus 3
}}

{{PMID Auto
|PMID=18165968
|Title=Identification of pharmacogenetic markers in smoking cessation therapy.
|OA=1
}}

{{PMID Auto
|PMID=18227835
|Title=Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking.
|OA=1
}}

{{PMID Auto
|PMID=18385676
|Title=Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
|OA=1
}}

{{PMID Auto
|PMID=18414406
|Title=Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence.
}}

{{PMID Auto
|PMID=18565990
|Title=Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence.
|OA=1
}}

{{PMID Auto
|PMID=18571741
|Title=Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research.
|OA=1
}}

{{PMID Auto
|PMID=18759969
|Title=In search of causal variants: refining disease association signals using cross-population contrasts.
|OA=1
}}

{{PMID Auto
|PMID=18780872
|Title=Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer.
|OA=1
}}

{{PMID Auto
|PMID=18957677
|Title=The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer.
|OA=1
}}

{{PMID Auto
|PMID=19005185
|Title=Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese.
}}

{{PMID Auto
|PMID=19010884
|Title=Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine.
|OA=1
}}

{{PMID Auto
|PMID=19029397
|Title=Nicotinic receptor gene variants influence susceptibility to heavy smoking.
|OA=1
}}

{{PMID Auto
|PMID=19064933
|Title=Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.
|OA=1
}}

{{PMID Auto
|PMID=19184766
|Title=A testable prognostic model of nicotine dependence.
|OA=1
}}

{{PMID Auto
|PMID=19238175
|Title=New insights into the genetics of addiction.
|OA=1
}}

{{PMID Auto
|PMID=19247474
|Title=Genome-wide and candidate gene association study of cigarette smoking behaviors.
|OA=1
}}

{{PMID Auto
|PMID=19300482
|Title=A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci.
|OA=1
}}

{{PMID Auto
|PMID=19330903
|Title=Gene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican-Americans.
|OA=1
}}

{{PMID Auto
|PMID=19390575
|Title=Lung cancer susceptibility model based on age, family history and genetic variants.
|OA=1
}}

{{PMID Auto
|PMID=19436041
|Title=Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes.
|OA=1
}}

{{PMID Auto
|PMID=19443489
|Title=Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5.
|OA=1
}}

{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}

{{PMID Auto
|PMID=19492010
|Title=The genetic components of alcohol and nicotine co-addiction: from genes to behavior.
|OA=1
}}

{{PMID Auto
|PMID=20485328
|Title=Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes.
|OA=1
}}

{{PMID Auto
|PMID=20529875
|Title=SPOT: a web-based tool for using biological databases to prioritize SNPs after a genome-wide association study.
|OA=1
}}

{{PMID Auto
|PMID=20548021
|Title=Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.
|OA=1
}}

{{PMID Auto
|PMID=20725741
|Title=Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity.
}}

{{PMID Auto
|PMID=20808433
|Title=Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a Korean population.
|OA=1
}}

{{PMID Auto
|PMID=20886544
|Title=Risk gene variants for nicotine dependence in the CHRNA5-CHRNA3-CHRNB4 cluster are associated with cognitive performance.
}}

{{PMID Auto
|PMID=21268243
|Title=Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy.
}}

{{PMID Auto
|PMID=21304900
|Title=Individual and cumulative effects of GWAS susceptibility loci in lung cancer: associations after sub-phenotyping for COPD.
|OA=1
}}

{{PMID Auto
|PMID=21335511
|Title=A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.
|OA=1
}}

{{PMID Auto
|PMID=21385908
|Title=Association of the nicotine metabolite ratio and CHRNA5/CHRNA3 polymorphisms with smoking rate among treatment-seeking smokers.
|OA=1
}}

{{PMID Auto
|PMID=21430647
|Title=The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment.
|OA=1
}}

{{PMID Auto
|PMID=21810735
|Title=Single nucleotide polymorphisms in CHRNA5 rs16969968, CHRNA3 rs578776, and LOC123688 rs8034191 are associated with heaviness of smoking in women in Northeastern Ontario, Canada.
}}

{{PMID Auto
|PMID=21856741
|Title=Functional characterization of the alpha5(Asn398) variant associated with risk for nicotine dependence in the alpha3beta4alpha5 nicotinic receptor.
|OA=1
}}

{{PMID Auto
|PMID=21862624
|Title=Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC.
}}

{{PMID Auto
|PMID=21955800
|Title=The polymorphism of the CHRNA5 gene and the strength of nicotine addiction in lung cancer and COPD patients.
}}

{{PMID Auto
|PMID=22028403
|Title=A case-control study of a sex-specific association between a 15q25 variant and lung cancer risk.
|OA=1
}}

{{PMID Auto
|PMID=22071378
|Title=Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=22102629
|Title=Dissection of the phenotypic and genotypic associations with nicotinic dependence.
|OA=1
}}

{{PMID Auto
|PMID=22223462
|Title=Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.
|OA=1
}}

{{PMID Auto
|PMID=22539395
|Title=Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.
|OA=1
}}

{{PMID Auto
|PMID=22544838
|Title=From Men to Mice: CHRNA5/CHRNA3, Smoking Behavior and Disease.
|OA=1
}}

{{GET Evidence
|gene=CHRNA5
|aa_change=Asp398Asn
|aa_change_short=D398N
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs16969968
|overall_frequency_n=2675
|overall_frequency_d=10758
|overall_frequency=0.248652
|n_genomes=18
|n_genomes_annotated=0
|n_haplomes=21
|n_articles=1
|n_articles_annotated=1
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|in_omim=Y
|in_pharmgkb=Y
|pph2_score=0.003
|nblosum100=-1
|autoscore=2
|webscore=N
|summary_short=Associated with early onset addiction to nicotine and with susceptibility to lung cancer.
}}

{{PMID Auto
|PMID=23196875
|Title=Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder
|OA=1
}}

{{PMID Auto
|PMID=23221128
|Title=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
|OA=1
}}

{{PMID Auto
|PMID=23232035
|Title=Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans
|OA=1
}}

{{PMID Auto
|PMID=23443019
|Title=Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56 307 individuals from the HUNT study in Norway
|OA=1
}}

{{PMID Auto
|PMID=23308091
|Title=A complex interplay between personality domains, marital status and a variant in CHRNA5 on the risks of cocaine, nicotine dependences and cocaine-induced paranoia
|OA=1
}}

{{PMID Auto
|PMID=24296975
|Title=Nicotine consumption is regulated by a human polymorphism in dopamine neurons
}}

{{PMID Auto
|PMID=24303001
|Title=Cis-Regulatory Variants Affect CHRNA5 mRNA Expression in Populations of African and European Ancestry
|OA=1
}}

{{PMID Auto
|PMID=22820273
|Title=Impact of human D398N single nucleotide polymorphism on intracellular calcium response mediated by alpha3beta4alpha5 nicotinic acetylcholine receptors.
|OA=1
}}

{{PMID Auto
|PMID=22884254
|Title=Association of nicotine dependence susceptibility gene, CHRNA5, with Parkinson's disease age at onset: gene and smoking status interaction.
}}

{{PMID Auto
|PMID=22914670
|Title=Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population.
}}

{{PMID Auto
|PMID=23178447
|Title=Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population.
}}

{{PMID Auto
|PMID=23334941
|Title=A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity.
|OA=1
}}

{{PMID Auto
|PMID=23358500
|Title=Variation in the alpha 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content.
}}

{{PMID Auto
|PMID=23404318
|Title=Interpreting joint SNP analysis results: when are two distinct signals really two distinct signals?
|OA=1
}}

{{PMID Auto
|PMID=23454887
|Title=Role of selected genetic variants in lung cancer risk in African Americans.
|OA=1
}}

{{PMID Auto
|PMID=23692359
|Title=CHRNA5-A3-B4 genetic variants alter nicotine intake and interact with tobacco use to influence body weight in Alaska Native tobacco users.
}}

{{PMID Auto
|PMID=25051068
|Title=Four SNPs in the CHRNA3/5 Alpha-Neuronal Nicotinic Acetylcholine Receptor Subunit Locus Are Associated with COPD Risk Based on Meta-Analyses
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}