Genotype × Environment Interaction in Smoking Behaviors: A Systematic Review.
BACKGROUND
There has been rapid growth in research exploring gene-environment interaction (G×E) contributing to smoking behaviors. Yet, no systematic review exists to date.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
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.
Elizabeth K
EK
Do
Department of Psychiatry and School of Medicine, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA.|Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA.|Massey Cancer Center, Virginia Commonwealth University, Richmond, VA.
Hermine H
HH
Maes
D004777:Environment; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D012907:Smoking