Do Elizabeth K, Maes Hermine H
Department of Psychiatry and School of Medicine, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA.
Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA.
Nicotine Tob Res. 2017 Apr 1;19(4):387-400. doi: 10.1093/ntr/ntw153.
There has been rapid growth in research exploring gene-environment interaction (G×E) contributing to smoking behaviors. Yet, no systematic review exists to date.
This article aims to review evidence on the contribution of G×E to the risk of smoking. Through a search of electronic databases (ie, Google Scholar, PubMed, ScienceDirect, and Elsevier) up until May 2014, 16 studies of G×E focused on smoking behaviors were identified. These studies were compared in terms of: research design and sample studied, measure of smoking behavior and environments used, genes explored, and G×E in relation to these factors.
Thirteen of 16 studies (81.2%) found at least one significant G×E association. Wide variation in analytic methods was found across studies, especially with respect to the phenotypes of interest, environmental measures used, and tests conducted to estimate G×E. Heterogeneity across studies made it difficult to compare findings and evaluate the strength of evidence for G×E.
G×E research on smoking contains studies that are methodologically different, making it difficult to assess the current state of the evidence. To decrease heterogeneity, we offer recommendations related to: (1) choice of measurement for environmental variables, (2) testing and reporting of main and interaction effects, (3) treatment of covariates, (4) reporting gene-environment correlation, and (5) conducting sensitivity analyses and checking for scaling artifacts. Continued study is needed to identify mechanisms by which genes and environmental factors combine to influence smoking behaviors.
No comprehensive review of G×E studies of smoking behavior has previously been published. The present article seeks to fill this gap by providing a comprehensive review of: how G×E has been defined, how twin and molecular genetic methodologies have been used to test for G×E, and which genes and environmental factors are associated with smoking behaviors. Variations in methodological approaches make it difficult to interpret and summarize findings, so recommendations for future research are provided as a means to more easily compare and replicate findings across studies.
探索基因 - 环境相互作用（G×E）对吸烟行为影响的研究迅速增加。然而，迄今为止尚无系统性综述。
本文旨在综述关于G×E对吸烟风险影响的证据。通过检索截至2014年5月的电子数据库（即谷歌学术、PubMed、ScienceDirect和爱思唯尔），确定了16项聚焦于吸烟行为的G×E研究。对这些研究在以下方面进行了比较：研究设计和研究样本、吸烟行为和所用环境的测量方法、探索的基因，以及与这些因素相关的G×E。
16项研究中的13项（81.2%）发现了至少一种显著的G×E关联。研究间分析方法差异很大，尤其是在感兴趣的表型、所用环境测量方法以及用于估计G×E的测试方面。研究间的异质性使得难以比较研究结果并评估G×E证据的强度。
关于吸烟的G×E研究包含方法上不同的研究，这使得难以评估当前的证据状况。为降低异质性，我们提出以下相关建议：（1）环境变量测量方法的选择；（2）主效应和交互效应的测试与报告；（3）协变量的处理；（4）基因 - 环境相关性的报告；（5）进行敏感性分析并检查尺度伪迹。需要持续研究以确定基因和环境因素共同影响吸烟行为的机制。
此前尚未发表过关于吸烟行为的G×E研究的全面综述。本文旨在填补这一空白，全面综述：G×E如何定义，如何使用双生子和分子遗传学方法测试G×E，以及哪些基因和环境因素与吸烟行为相关。方法学方法的差异使得难以解释和总结研究结果，因此提供未来研究建议，作为更轻松地在不同研究中比较和重复研究结果的一种手段。
