We analyzed self-reported first use of tobacco, alcohol, cannabis, inhalants, and other substances obtained during the first wave when the subjects were on average between 16 and 17 years old. The sample was limited to Caucasians due to allele frequency differences across different ethnic groups (Schlaepfer et al. 2008), and to subjects with available genetic data. Subjects had been previously typed for ten SNPs on CHRNA5/A3/B4 including rs16969968 and nine SNPs that were examined by Schlaepfer et al. (2008) in two samples, a Colorado sample and the National Youth Survey sample, that were independent of the Add Health sample used here. Hence, the current study was designed to replicate previous results, and to extend findings by focusing on population heterogeneity in the phenotype. Using a subset of a population data set provides a wide dispersion of the phenotype measures, and therefore affords the possibility of capturing potential heterogeneity in the phenotype, and of modeling the association of SNPs with subgroup differences. A second aim was to obtain more detailed information concerning the specificity of the CHRNA5/A3/B4 gene cluster with respect
