Although the genetic and environmental influences on cigarette-smoking behavior have been well established, translation of this research into useful risk-factor targets for public health intervention is lacking. Among the reasons is the complex nature of smoking behaviors, which are influenced by multiple genetic and environmental risk factors, each having very subtle effects. Related is the limitation of current statistical and genetic methodologies to successfully identify novel, replicable variants in relatively small (n <1,000) samples. Despite these limitations, evidence for the influence of gene–environment interactions on smoking behaviors is mounting, both from molecular genetic studies and epidemiologic studies. Polygenic risk scores are an aggregate measure of genetic variants that influence the trait of interest and therefore do not require the rigorous statistical test corrections required for GWAS. Importantly, these methods allow for the examination of specific environmental risk factors and how genetic influences may change as a function of the environmental risk factor. These risk factors, and how they can diminish or exacerbate genetic influences on cigarette use, have important implications for public health interventions as they are potentially modifiable risk factors.
