There are several limitations of this study as well. First, because of the sample size, this study is limited in the potential strength of the association signal. A power calculation indicated 78% power to detect the main effects, given the parameters of this study. However, the rich environmental data available on this sample provide the opportunity to refine genetic associations discovered and validated in larger, better powered samples. Second, this polygenic risk score is largely driven by a single variant (CHRNA5 SNP rs203652) and therefore is not truly polygenic in nature. However, predictive power is gained from the inclusion of the other genetic variants in the risk score. Finally, the present analysis uses data available at a single time point, using retrospective reports of smoking, traumatic life events and neighborhood characteristics.
