To extend our observation on the nicotine-related behavioral effects of FKBP5 variation, we examined the association of rs3800373 to nicotine withdrawal symptoms in a population of current EA and AA smokers (EA and AA; total n=3821) that were recruited for genetic studies of substance dependence. The demographic characteristics and major psychiatric comorbidities are shown in Table S2 (Supplemental Information). We examined subjects’ reports of any DSM-IV nicotine withdrawal symptom and those lasting for 24 hours. Subjects with at least one rs3800373*C allele reported fewer nicotine withdrawal symptoms than those homozygous for rs3800373*A (Figure 1B) (main effect for group: Pmeta < 0.05) and fewer nicotine withdrawal symptoms that lasted for 24 hours (main effect for group: Pmeta < 0.005). Mean withdrawal counts for EA and AA genotype groups from each array are shown in Table S3 (Supplemental Information). In this analysis, comorbid anxiety or depression was used as a covariate in the regression models to control for the effects of anxiety and depression on the severity of withdrawal symptoms.
