Although investigators have examined gene–environment interactions in smoking using individual genetic variants (candidate genes) or latent genetic influences (twin studies), no study to our knowledge has used polygenic risk scores in the context of GxE for smoking behaviors. A polygenic risk score aggregates measured genetic variants to more closely reflect the underlying structure of complex traits; multiple genetic variants of small effect that act in conjunction with each other (epistasis) and the external environment (GxE). Further, as a polygenic risk score aggregates specific genetic variants, it enables the examination of social factors that may moderate underlying genetic influences. In this study, we expand upon the literature by examining the interaction between an aggregate measure of genetic risk for cigarette smoking and three environmental exposures that have previously been associated with increased substance use: traumatic life events, neighborhood social cohesion and neighborhood physical disorder. In an effort to model the genetic architecture of smoking behaviors in African Americans, the first aim of this study is to use the genetic variants associated (P-value <5 × 10−7) with number of cigarettes smoked per
