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

doi:10.1016/j.tins.2016.10.005

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 journal › Article (Academic Journal) › peer-review

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Abstract

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 language	English
Pages (from-to)	851–861
Number of pages	11
Journal	Trends in Neurosciences
Volume	39
Issue number	12
Early online date	18 Nov 2016
DOIs	https://doi.org/10.1016/j.tins.2016.10.005
Publication status	Published - Dec 2016

Research Groups and Themes

Brain and Behaviour
Tobacco and Alcohol

Keywords

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

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10.1016/j.tins.2016.10.005

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MRC UoB UNITE Unit - Programme 6
Munafo, M. R. (Principal Investigator) & Munafo, M. R. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

Cite this

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title = "The CHRNA5-A3-B4 gene cluster and smoking: From discovery to therapeutics",

abstract = "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{\textquoteright} 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. ",

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

author = "Glenda Lassi and Amy Taylor and Nicholas Timpson and {J Kenny}, Paul and {J Mather}, Robert and Timothy Eisen and Marcus Munafo",

year = "2016",

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T2 - From discovery to therapeutics

AU - Lassi, Glenda

AU - Taylor, Amy

AU - Timpson, Nicholas

AU - J Kenny, Paul

AU - J Mather, Robert

AU - Eisen, Timothy

AU - Munafo, Marcus

PY - 2016/12

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AB - 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.

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KW - phenotype definition

KW - tobacco-related disorders

KW - precision medicine

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DO - 10.1016/j.tins.2016.10.005

M3 - Article (Academic Journal)

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

Abstract

Research Groups and Themes

Keywords

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Projects

MRC UoB UNITE Unit - Programme 6

MRC UoB UNITE Unit - programme 3

Cite this