The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco

Hum Mol Genet. 2008 Mar 1;17(5):724-34. doi: 10.1093/hmg/ddm344. Epub 2007 Nov 30.


Neuronal nicotinic acetylcholine receptors have been implicated in various measures of nicotine dependence. In this paper, we present findings from an exploratory study of single nucleotide polymorphisms (SNPs) in the CHRNB3 and CHRNA6 genes with tobacco and alcohol phenotypes, including frequency of use and three subjective response factors occurring shortly after initiation of use. Subjects were 1056 ethnically diverse adolescents ascertained from clinical and community settings. The most significant associations were found between two CHRNB3 SNPs (rs4950 and rs13280604) and the three subjective response factors to initial tobacco use. These findings were replicated in a separate community sample of 1524 families participating in the National Longitudinal Study of Adolescent Health. Both CHRNB3 SNPs were found to be associated with similar measures of subjective response to tobacco. These results indicate that early subjective response to nicotine may be a valuable endophenotype for genetic studies aimed at uncovering genes contributing to nicotine use and addiction.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Americans / statistics & numerical data
  • Alcoholism / genetics
  • Alleles
  • Data Interpretation, Statistical
  • Female
  • Gene Frequency
  • Genetic Markers
  • Genetic Variation
  • Haplotypes
  • Hispanic or Latino / statistics & numerical data
  • Humans
  • Linear Models
  • Male
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, Nicotinic / genetics*
  • Siblings
  • Smoking / genetics
  • Tobacco Use Disorder / genetics*
  • Whites / statistics & numerical data


  • CHRNA6 protein, human
  • CHRNB4 protein, human
  • Genetic Markers
  • Nerve Tissue Proteins
  • Receptors, Nicotinic