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

doi:10.1016/j.tins.2016.10.005

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 journal › Review article › peer-review

60 Scopus citations

Abstract

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 language	English
Pages (from-to)	851-861
Number of pages	11
Journal	Trends in Neurosciences
Volume	39
Issue number	12
DOIs	https://doi.org/10.1016/j.tins.2016.10.005
State	Published - 1 Dec 2016

Keywords

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

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10.1016/j.tins.2016.10.005

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title = "The CHRNA5–A3–B4 Gene Cluster and Smoking: From Discovery to Therapeutics",

abstract = "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{\textquoteright} 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.",

keywords = "CHRNA5–A3–B4, phenotype definition, precision medicine, smoking behaviour, tobacco-related disorders",

author = "Glenda Lassi and Taylor, {Amy E.} and Timpson, {Nicholas J.} and Kenny, {Paul J.} and Mather, {Robert J.} and Tim Eisen and Munaf{\`o}, {Marcus R.}",

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AU - Taylor, Amy E.

AU - Timpson, Nicholas J.

AU - Kenny, Paul J.

AU - Mather, Robert J.

AU - Eisen, Tim

AU - Munafò, Marcus R.

PY - 2016/12/1

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AB - 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.

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KW - phenotype definition

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KW - smoking behaviour

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

Abstract

Keywords

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