The CHRNA5–A3–B4 Gene Cluster and Smoking: From Discovery to Therapeutics

Glenda Lassi, Amy E. Taylor, Nicholas J. Timpson, Paul J. Kenny, Robert J. Mather, Tim Eisen, Marcus R. Munafò

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations


Genome-wide association studies (GWASs) have identified associations between the CHRNA5–CHRNA3–CHRNB4 gene cluster and smoking heaviness and nicotine dependence. Studies in rodents have described the anatomical localisation and function of the nicotinic acetylcholine receptors (nAChRs) 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. GWASs 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 medication 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
StatePublished - 1 Dec 2016


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


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