The CHRNA5-A3-B4 gene cluster and smoking: From discovery to therapeutics

Glenda Lassi, Amy Taylor, Nicholas Timpson, Paul J Kenny, Robert J Mather, Timothy Eisen, Marcus Munafo

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)
331 Downloads (Pure)


Genome wide association studies (GWAS) have identified associations between the CHRNA5-CHRNA3-CHRNB4 gene cluster and smoking heaviness and nicotine dependence. Studies in rodents have described the anatomical localization and function of the nicotinic acetylcholine receptors formed by the subunits encoded by this gene cluster. Further investigations that complemented these studies highlighted the variability of individuals’ smoking behaviours and their ability to adjust nicotine intake. GWAS of smoking-related health outcomes have also identified this signal in the CHRNA5-CHRNA3-CHRNB4 gene cluster. This insight underpins approaches to strengthen causal inference in observational data. Combining genetic and mechanistic studies of nicotine dependence and smoking heaviness may reveal novel targets for medications development. Validated targets can inform genetic therapeutic interventions for smoking cessation and tobacco-related diseases.
Original languageEnglish
Pages (from-to)851–861
Number of pages11
JournalTrends in Neurosciences
Issue number12
Early online date18 Nov 2016
Publication statusPublished - Dec 2016

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol


  • CHRNA5-A3-B4
  • smoking behaviour
  • phenotype definition
  • tobacco-related disorders
  • precision medicine

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