Lassi Glenda, Taylor Amy E, Timpson Nicholas J, Kenny Paul J, Mather Robert J, Eisen Tim, Munafò Marcus R
UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK; Oncology Translational Medicine Unit, Early Clinical Development, AstraZeneca, Cambridge, UK.
UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Trends Neurosci. 2016 Dec;39(12):851-861. doi: 10.1016/j.tins.2016.10.005. Epub 2016 Nov 18.
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.
全基因组关联研究（GWASs）已确定CHRNA5-CHRNA3-CHRNB4基因簇与吸烟量及尼古丁依赖之间的关联。对啮齿动物的研究描述了由该基因簇编码的亚基所形成的烟碱型乙酰胆碱受体（nAChRs）的解剖定位和功能。补充这些研究的进一步调查突出了个体吸烟行为的变异性及其调节尼古丁摄入量的能力。与吸烟相关健康结局的GWASs也在CHRNA5-CHRNA3-CHRNB4基因簇中发现了这一信号。这一见解为加强观察性数据中的因果推断方法提供了支持。将尼古丁依赖和吸烟量的遗传学与机制研究相结合，可能会揭示药物开发的新靶点。经过验证的靶点可为戒烟及烟草相关疾病的基因治疗干预提供依据。
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