We investigated age of onset of nicotine and alcohol use and their association with SNPs in the CHRNA5/A3/B4 gene cluster. Since especially mouse models indicated involvement of subunits in a broader range of substance use behaviors, we investigated three additional substances or substance groups in an attempt to explore the specificity of the CHRNA5/A3/B4 gene cluster in substance use initiation. The three additional phenotypes were age of initiation of cannabis, inhalants, and “other substances”. “Other substances” included LSD, PCP, ecstasy, and amphetamines.