rs8040868

This is a synonymous variant in the CHRNA3 gene — it does not change the protein's amino acid sequence.

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GWAS Catalog Trait Associations (11)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

chronic obstructive pulmonary disease

Zhou W et al. “Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.” Cell Genomics 2(10):100192 (2022)
Allele C
OR 0.10
p 7.0e-60
N 1,392,366
Meta-analysisLarge GWAS
multi-ancestry
Kim W et al. “Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.” American Journal of Epidemiology 190(5):875-885 (2021)
Allele C
OR 1.07
p 2.0e-8
N 200,766
Large GWAS
European

smoking status measurement, chronic obstructive pulmonary disease

Kim W et al. “Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.” American Journal of Epidemiology 190(5):875-885 (2021)
Allele C
OR —
p 8.0e-24
N 200,766
Large GWAS
European

cigarettes per day measurement

Xu K et al. “Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.” Nature Communications 11(1):5302 (2020)
Allele C
OR —
β 0.044
p 2.0e-20
N 77,515
Meta-analysisLarge GWAS
European
Liu M et al. “Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.” Nature Genetics 51(2):237-244 (2019)
Allele C
OR 0.02
p 2.0e-10
N 377,334
Large GWAS
European

atherosclerosis

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele T
OR 0.08
p 5.0e-16
N 426,526
Major Consortium StudyLarge GWAS
European

family history of lung cancer

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele T
OR 0.10
p 3.0e-15
N 315,668
Major Consortium StudyLarge GWAS
European

lung carcinoma, family history of lung cancer

Byun J et al. “Genome-wide association study of familial lung cancer.” Carcinogenesis 39(9):1135-1140 (2018)
Allele C
OR 1.33
p 4.0e-13
N 35,953
Large GWAS
European

lung disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele T
OR 0.07
p 3.0e-12
N 427,399
Major Consortium StudyLarge GWAS
European
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ClinVar annotation

Benign★★★☆
3 submitters2 publications

Urinary bladder, atony of

View on ClinVar →
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Research that mentions this SNP (3)

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Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene cluster with nicotine dependence in African and European Americans
AssociationN=2,037Ming D. Li et al.(2010)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Family-based association analysis of 22 SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster on chromosome 15 with nicotine dependence in African Americans (N=1053) and European Americans (N=515). Individual SNP analyses showed nominal associations for rs1317286 and rs8040868 in CHRNA3 with smoking quantity and Heaviness Smoking Index (P=0.017–0.05), though none survived correction for multiple testing. Haplotype analysis identified significant associations with nicotine dependence measures before correction in both ethnic groups. Gene-gene interaction analysis using pedigree-based generalized multifactor dimensionality reduction detected significant interactions within CHRNA3 and among all three genes in African Americans and combined samples (P=0.002–0.045).

Traits studied:Fagerström Test for Nicotine DependenceHeaviness of Smoking IndexNicotine dependenceSmoking quantity
PubMedDOIMetascience Observatory
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Risk gene variants for nicotine dependence in the CHRNA5–CHRNA3–CHRNB4 cluster are associated with cognitive performance
AssociationN=492Georg Winterer et al.(2010)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This population-based study examined natural selection on nicotinic receptor gene clusters (CHRNB3-A6 on chromosome 8 and CHRNA5-A3-B4 on chromosome 15) using 1000 Genomes data from three populations. Using Tajima's D and integrated haplotype score (iHS) tests, the authors found strong evidence for positive selection in the CHRNB3-A6 region and moderate evidence in CHRNA5-A3-B4. These regions harbor variants previously associated with nicotine dependence (rs16969968, rs1451240) and cocaine dependence. To understand the target of selection, the authors tested variants in COGA subjects (N=492) for association with cognitive phenotypes (WAIS tests) and found one significant association: rs7017612 with WAIS Digit Symbol score (β=0.43, p=0.003), suggesting memory and learning may be the driving force behind selection.

Traits studied:Alcohol dependenceCocaine dependenceCognitive functionLearningMemoryNicotine dependenceProcessing speed
PubMedDOIMetascience Observatory
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Identification of pharmacogenetic markers in smoking cessation therapy
AssociationN=436Heitjan DF et al.(2008)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This Bayesian pharmacogenetic analysis of a bupropion vs placebo smoking cessation trial (n=436 European ancestry participants) identified four SNPs with pharmacogenetic relevance from 59 candidate SNPs in nicotinic acetylcholine receptor genes. The strongest signal was rs871058 in CHRNA5, which showed treatment-by-SNP interaction effects on 7-day smoking cessation rates. Bayesian hypothesis testing proved more conservative than unadjusted frequentist tests but less so than multiplicity-corrected tests, with no control SNPs showing significant associations.

Traits studied:Response to bupropion therapySmoking cessationTobacco dependence
PubMedDOIMetascience Observatory

About CHRNA3

This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

View all CHRNA3 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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