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

被引：56

作者：

Lassi, Glenda ^{[1
,2
]}

Taylor, Amy E. ^{[1
,3
]}

Timpson, Nicholas J. ^{[3
]}

Kenny, Paul J. ^{[4
,5
]}

Mather, Robert J. ^{[6
]}

Eisen, Tim ^{[2
,7
]}

Munafo, Marcus R. ^{[1
,3
]}

机构：

[1] Univ Bristol, Sch Expt Psychol, UK Ctr Tobacco & Alcohol Studies, Bristol, Avon, England

[2] AstraZeneca, Early Clin Dev, Oncol Translat Med Unit, Cambridge, England

[3] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[4] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Expt Therapeut Inst, New York, NY 10029 USA

[6] AstraZeneca, Neurosci IMED, Cambridge, MA USA

[7] Univ Cambridge, Dept Oncol, Cambridge, England

来源：

TRENDS IN NEUROSCIENCES | 2016年 / 39卷 / 12期

基金：

英国经济与社会研究理事会; 英国医学研究理事会;

关键词：

NICOTINIC ACETYLCHOLINE-RECEPTORS; HIGH TOBACCO CONSUMPTION; MENDELIAN RANDOMIZATION; LUNG-CANCER; RISK-FACTOR; DEPENDENCE; SCHIZOPHRENIA; ASSOCIATION; SUBUNIT; 15Q25;

D O I：

10.1016/j.tins.2016.10.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：851 / 861

页数：11

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