Single marker Genotype x Phenotype analysis was done using the statistical genetics software FBAT-PC (Lange et al., 2004a), which allows one to generate a maximally heritable composite phenotype for each SNP from a collection of multiple phenotypes. This data-driven approach provides a way to minimize multiple testing of phenotypes in the context of multiple SNPs and was derived from methods originally developed by Fulker et al. (Fulker et al., 1999). A maximally heritable composite phenotype is generated using information obtained from the between-family association for each SNP. This composite phenotype is tested subsequently for genetic association using the within-family association test, which is statistically independent of the between-family information (Lange et al., 2004a). The six SNPs in the CHRNB3-CHRNA6 region were tested using FBAT-PC to form a composite of four quantitative alcohol phenotypes: average number of drinks, number of blackouts, total number of DSM-IV abuse and dependence symptoms, and number of unsuccessful quit attempts. The four phenotypes were chosen to capture quantitative measures of alcohol-specific behaviors. It is worth noting that the last three of these phenotypes are lifetime measures
