Smokers with low FKBP5 mRNA levels reported lower levels of “negative” effects in response to nicotine than those with high FKBP5 mRNA (group-by-dose interaction: F(2,762)=5.62; P<0.005) (Figure 2A). The association of FKBP5 mRNA-by-dose to “negative” effects was independent of rs3800373 genotype. In a regression model that included genotype and genotype -by-FKBP5 mRNA, there was no significant main (or interactive) effect of genotype, while the FKBP5 mRNA-by-dose term remained significant. Likewise, including baseline cortisol levels, array number (1-4), cigarette pack-years, and RNA Integrity Number as covariates in the model had little effect on the p value for the FKBP5 mRNA-by-dose term.