lifetime maximum tobacco consumption; and regular smokers with high ND (n=229, 150 men and 79 women), defined as those who smoked for 5 years or more and had an FTQ score between 7 and 11. This 3-group design was to evaluate separately the influence of CNR1 on SI and ND, 2 measurements with overlapping but not identical genetic effects.5,46 To estimate the influence of CNR1 on SI, we compared the allele frequencies of testing SNPs between the nonsmokers and regular smokers (which included both the low -and high-ND groups). To estimate the influence of CNR1 on ND, we compared the allele frequencies between the low- and high-ND groups. Smokers with FTQ scores between 2 and 7 were not used in this dichotomized design. The second sample, denoted as the Virginia Study of Anxiety and Neuroticism (VAANX), was a sample initially selected for the study of anxiety and neuroticism. We used the software package Mx (http://www.vcu.edu/mx/) to perform a multivariate genetic analysis to identify a latent phenotype that reflected genetic covariation (ie, shared genetic susceptibility) across the 6 phenotypes (major depressive disorder, generalized anxiety disorder, panic disorder, agoraphobia, social phobia, and neuroticism [Hettema et al47 provide the details]). The inclusion criterion
