rs2236196
This is a regulatory region variant variant in the CHRNA4 gene.
▶GWAS Catalog Trait Associations (1)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (1)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
smoking cessation
▶ClinVar annotation
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE); Autosomal dominant nocturnal frontal lobe epilepsy 1; Tobacco addiction, susceptibility to
View on ClinVar →▶Research that mentions this SNP (4)
▶Association ofCHRNA4polymorphisms with smoking behavior in two populationsAssociationN=3,039Shizhong Han et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This candidate gene association study examined five CHRNA4 SNPs in 1,249 European-Americans and 1,790 African-Americans to evaluate associations with smoking behavior. The synonymous SNP rs1044394 was significantly associated with nicotine dependence (DSM-IV ND: P=0.001; FTND: P=0.01) and remained significant after multiple testing correction for ND (P=0.033). Rs2236196 was associated with cigarettes per day (P=0.003), with similar association patterns observed in both ancestry groups.
▶Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genesAssociationN=1,929Nancy L. Saccone et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This comprehensive association study of 226 SNPs across all 16 nicotinic receptor subunit (CHRN) genes identified four distinct genetic loci significantly associated with nicotine dependence in 1050 cases and 879 controls of European descent. The two most significant associations were rs16969968 (CHRNA5, non-synonymous, p=0.00013, OR=1.30) and rs578776 (CHRNA3, p=0.00011, OR=1.34) in the CHRNA5-CHRNA3-CHRNB4 cluster; one locus in the CHRNB3-CHRNA6 cluster tagged by rs13277254 (p=0.00010); and a novel locus in the CHRND-CHRNG cluster tagged by rs12466358 (p=0.00027). Joint analyses confirmed statistical independence of the two CHRNA5-CHRNA3-CHRNB4 signals.
▶Identification of pharmacogenetic markers in smoking cessation therapyAssociationN=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.
▶CHRNA4 and Tobacco DependenceAssociationN=316Kent E. Hutchison et al.(2007)· Archives of General Psychiatry
This transdisciplinary pharmacogenetic study examined CHRNA4 gene variants (rs6122429, rs2236196) in tobacco dependence. The study included 316 smokers for laboratory assessments and 353 participants in a clinical smoking cessation trial. Both SNPs showed associations with subjective responses to smoking in laboratory settings, and rs2236196 was associated with smoking cessation outcomes, providing evidence that CHRNA4 variants are functional at the biological level and influence nicotine dependence phenotypes.
About CHRNA4
This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
View all CHRNA4 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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