{{Rsnum
|rsid=1051730
|Gene=CHRNA3
|Chromosome=15
|position=78601997
|Orientation=plus
|ReferenceAllele=C
|GMAF=0.1933
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=smoking and drinking
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=CHRNA3
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 38.9 | 45.1 | 15.9
| HCB | 94.9 | 5.1 | 0.0
| JPT | 95.6 | 4.4 | 0.0
| YRI | 79.6 | 19.7 | 0.7
| ASW | 68.4 | 31.6 | 0.0
| CHB | 94.9 | 5.1 | 0.0
| CHD | 92.7 | 7.3 | 0.0
| GIH | 63.0 | 31.0 | 6.0
| LWK | 90.9 | 9.1 | 0.0
| MEX | 62.1 | 32.8 | 5.2
| MKK | 77.6 | 21.8 | 0.6
| TSI | 36.3 | 45.1 | 18.6
| HapMapRevision=28
}}[[rs1051730]], also known as D398N, is a SNP in the nicotinic acetylcholine receptor alpha 3 subunit [[CHRNA3]] gene.

In two recent (2008) studies, together comprising over 6,000 [[lung cancer]] patients of European ancestry, the [[rs1051730]](T) allele was very significantly associated with increased risk. Having one copy (i.e. being a [[rs1051730]](C;T) genotype) increased risk for [[lung cancer]] about 1.3x, and having two copies ([[rs1051730]](T;T) individuals) represented 1.8x increased risk. Up to 14% of [[lung cancer]] incidence may be attributable to this allele.[PMID 18385738, PMID 18385676]

An independent study published at the same time concluded that (T) allele carriers for SNP [[rs1051730]] are not at higher risk of becoming smokers compared to (C) carriers. However, if they do smoke, (T) carriers are quite likely to smoke more cigarettes than (C) carriers, and as an apparent consequence, they are at higher risk for [[lung cancer]] as reported in this and other studies. This study therefore links [[rs1051730]] directly to [[nicotine dependence]], and indirectly to [[lung cancer]]. {{PMID|18385739}}

According to DeCODE, the CC genotype at [[rs1051730]] is associated with 0.88x risk of [[peripheral arterial disease]] (PAD). {{PMID|18385739}}

Note: publications tend to refer to the risk allele as "A", however, the orientation reported for [[rs1051730]] in [[dbSNP]] is for the opposite strand, so in keeping with reporting all SNPs in the orientation published in dbSNP, SNPedia refers to this same risk allele as the (T) allele. 

[http://blog.23andme.com/2008/12/09/snpwatch-two-vices-one-snp-%E2%80%94-drinking-and-smoking-behavior-both-linked-to-nicotine-receptor-genes/ 23andMe blog] (T;T) once more smoke per day.

{{PMID|19064933|OA=1
}} [[rs1051730]] influences how much alcohol it takes to have you feel a buzz. More professorially: [[rs1051730]] influences the level of response to alcohol intake, as measured by body sway after having a 10am "3 drink challenge". [[rs1051730]](T;T) individuals respond slower to alcohol, which generally is considered to actually increase their long-term risk of alcohol abuse.

[http://blog.23andme.com/2009/05/15/snpwatch-genetic-variation-may-make-it-harder-for-expectant-moms-to-quit-smoking/ 23andMe blog] (T;T) makes it harder to quit smoking

{{GWAS Summary
|SNP=rs1051730
|PubMedID=18385739
|Condition=Nicotine dependence
|Gene=CHRNA3,CHRNA5,CHRNB4
|Risk Allele=T
|pValue=6.00E-020
|OR=0.1
|95CI=0.08-0.12) increase in cigarettes per da
}}
{{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 GWAS
|PMID=18978790
|Trait=Lung cancer
|Title=Lung cancer susceptibility locus at 5p15.33
|RiskAllele=A
|Pval=1E-15
|OR=1.35
|ORtxt=[1.25-1.45]
|OA=1
}}
{{PMID Auto
|PMID=19465454
|Title=The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung
}}

{{omim
|desc=LUNG CANCER SUSCEPTIBILITY 2; LNCR2
|id=612052
|rsnum=1051730
}}

{{omim
|desc=TOBACCO ADDICTION, SUSCEPTIBILITY TO
|id=188890
|rsnum=1051730
}}

{{omim
|id=118503
|desc=CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 3; CHRNA3
|rsnum=1051730
}}
{{PMID Auto
|PMID=19641473
|Title=Racial Differences in the Association Between SNPs on 15q25.1, Smoking Behavior, and Risk of Non-small Cell Lung Cancer
|OA=1
}}
{{PMID Auto
|PMID=19733931
|Title=Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients
}}

{{PMID Auto GWAS
|PMID=19836008
|Trait=Lung adenocarcinoma
|Title=A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma
|RiskAllele=T
|Pval=2E-51
|OR=1.31
|ORtxt=[1.27-1.36]
|OA=1
}}

{{PharmGKB
|RSID=rs1051730
|Name_s=
|Gene_s=CHRNA3
|Feature=
|Evidence=PubMed ID:18978790; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Lung cancer susceptibility locus at 5p15.33. (Initial Sample Size: 2,971 cases, 3,746 controls; Replication Sample Size: 2,899 cases, 5,573 controls); (Region: 15q25.1; Reported Gene(s): Intergenic; Risk Allele: rs1051730-A); (p-value= 0.000000000000001).This variant is associated with Lung cancer.
|Drugs=
|Drug Classes=
|Diseases=Lung Neoplasms
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740764
}}
{{PMID Auto
|PMID=19132693
|Title=Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence
|OA=1
}}

{{PMID Auto
|PMID=20068085
|Title=Analysis of Genetic Variants in Never-Smokers with Lung Cancer Facilitated by an Internet-Based Blood Collection Protocol: A Preliminary Report
|OA=1
}}

{{PMID Auto
|PMID=20418890
|Title=Genome-wide meta-analyses identify multiple loci associated with smoking behavior
|OA=1
}}
{{PMID Auto GWAS
|PMID=20418889
|Trait=Smoking behavior
|Title=Meta-analysis and imputation refines the association of 15q25 with smoking quantity
|RiskAllele=G
|Pval=2E-66
|OR=0.08
|ORtxt=[0.07-0.09] unit decrease
|OA=1
}}
{{PMID Auto GWAS
|PMID=20418888
|Trait=Smoking behavior
|Title=Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
|RiskAllele=A
|Pval=2E-69
|OR=0.80
|ORtxt=[0.70-0.90] CPD increase
|OA=1
}}
{{PMID Auto
|PMID=20554942
|Title=Nicotinic Acetylcholine Receptor Region on Chromosome 15q25 and Lung Cancer Risk Among African Americans: A Case-Control Study
|OA=1
}}
{{PMID Auto
|PMID=20564069
|Title=Mediating effects of smoking and chronic obstructive pulmonary disease on the relation between the CHRNA5-A3 genetic locus and lung cancer risk
|OA=1
}}
{{PMID Auto
|PMID=20393456
|Title=Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers
|OA=1
}}

{{PharmGKB
|RSID=rs1051730
|Name_s=CHRNA3:Gly394Gly
|Gene_s=CHRNA3
|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 rs16969968, is similarly associated with early onset nicotine dependence.
|Drugs=nicotine
|Drug Classes=
|Diseases=Tobacco Use Disorder
|Curation Level=Curated
|PharmGKB Accession ID=PA162168239
}}

{{PharmGKB
|RSID=rs1051730
|Name_s=
|Gene_s=CHRNA3
|Feature=
|Evidence=PubMed ID:18385676; PubMed ID:18385739
|Annotation=This variant is associated with nicotine dependence, lung cancer and peripheral arterial disease.
|Drugs=nicotine
|Drug Classes=
|Diseases=Lung Neoplasms; Peripheral Vascular Diseases
|Curation Level=Curated
|PharmGKB Accession ID=PA161615727
}}

{{PharmGKB
|RSID=rs1051730
|Name_s=
|Gene_s=CHRNA3
|Feature=
|Evidence=PubMed ID:18385739; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: A variant associated with nicotine dependence, lung cancer and peripheral arterial disease (Initial Sample Size: 10,995 smokers; Replication Sample Size: 4,848 smokers; Risk Allele: rs1051730-T).
|Drugs=
|Drug Classes=
|Diseases=Tobacco Use Disorder
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356775
}}
{{PMID Auto
|PMID=21248747
|Title=Association of a variant in the CHRNA5-A3-B4 gene cluster region to heavy smoking in the Italian population
|OA=1
}}

{{omim
|id=118503
|rsnum=1051730
|variant=0001
}}

{{PMID Auto
|PMID=21511889
|Title=Variant Within the Promoter Region of the CHRNA3 Gene Associated With FTN Dependence Is Not Related to Self-reported Willingness to Quit Smoking
}}

{{PMID Auto
|PMID=21646606
|Title=Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study
}}

{{PMID Auto
|PMID=21645942
|Title=Association of smoking with tumor size at diagnosis in non-small cell lung cancer
|OA=1
}}

{{PMID Auto
|PMID=21685187
|Title=Genome-wide association study of smoking behaviours in patients with COPD
|OA=1
}}

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

{{PMID Auto
|PMID=22441734
|Title=CHRNA3 genotype, nicotine dependence, lung function and disease in the general population
}}

{{PMID Auto
|PMID=22687325
|Title=The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study
}}

{{PMID Auto
|PMID=18385721
|Title=With a coarse-tooth comb
}}

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

{{PMID Auto
|PMID=17135278
|Title=Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.
|OA=1
}}

{{PMID Auto
|PMID=18519524
|Title=Variants in nicotinic receptors and risk for nicotine dependence.
|OA=1
}}

{{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=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=19300500
|Title=A genome-wide association study of pulmonary function measures in the Framingham Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=19423719
|Title=Update in lung cancer 2008.
|OA=1
}}

{{PMID Auto
|PMID=19429911
|Title=A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy.
|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=19569043
|Title=Genome-wide association studies and the genetic dissection of complex traits.
|OA=1
}}

{{PMID Auto
|PMID=19628476
|Title=Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15.
|OA=1
}}

{{PMID Auto
|PMID=19639606
|Title=Correcting "winner's curse" in odds ratios from genomewide association findings for major complex human diseases.
|OA=1
}}

{{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=19750184
|Title=Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
|OA=1
}}

{{PMID Auto
|PMID=19800047
|Title=Integration of genomic and genetic approaches implicates IREB2 as a COPD susceptibility gene.
|OA=1
}}

{{PMID Auto
|PMID=20007924
|Title=The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema.
}}

{{PMID Auto
|PMID=20010834
|Title=Genome-wide association study identifies five loci associated with lung function.
|OA=1
}}

{{PMID Auto
|PMID=20010835
|Title=Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.
|OA=1
}}

{{PMID Auto
|PMID=20395203
|Title=A second genetic variant on chromosome 15q24-25.1 associates with lung cancer.
|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=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=21081471
|Title=Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.
|OA=1
}}

{{PMID Auto
|PMID=21168125
|Title=TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood.
|OA=1
}}

{{PMID Auto
|PMID=21232152
|Title=Epidemiology, radiology, and genetics of nicotine dependence in COPD.
|OA=1
}}

{{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=21320324
|Title=The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study.
|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=21690317
|Title=CHRNA3 rs1051730 genotype and short-term smoking cessation.
|OA=1
}}

{{PMID Auto
|PMID=21697764
|Title=Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer.
|OA=1
}}

{{PMID Auto
|PMID=21747048
|Title=Relationship between CYP2A6 and CHRNA5-CHRNA3-CHRNB4 variation and smoking behaviors 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=22544838
|Title=From Men to Mice: CHRNA5/CHRNA3, Smoking Behavior and Disease.
|OA=1
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1051730
|overall_frequency_n=2901
|overall_frequency_d=10758
|overall_frequency=0.26966
|n_genomes=19
|n_genomes_annotated=0
|n_haplomes=22
|n_articles=0
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=22701590
|Title=Strong association between two polymorphisms on 15q25.1 and lung cancer risk: a meta-analysis
|OA=1
}}

[[Peripheral Artery Disease]]

{{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=23249876
|Title=Nicotinic acetylcholine receptor variation and response to smoking cessation therapies
|OA=1
}}

{{PMID Auto
|PMID=23056235
|Title=Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese
|OA=1
}}

{{PMID Auto
|PMID=24254305
|Title=Quantitative assessment of the influence of common variations (rs8034191 and rs1051730) at 15q25 and lung cancer risk
}}

{{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=22956269
|Title=Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.
|OA=1
}}

{{PMID Auto
|PMID=23299987
|Title=Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility.
|OA=1
}}

{{PMID Auto
|PMID=23604333
|Title=The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism.
}}

{{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
}}

{{PMID Auto
|PMID=25073350
|Title=[Genetic aspects of occupational chronic obstructive lung disease under exposure to various risk factors]
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}