Quantitative trait analysis was performed in QTDT (Abecasis et al., 2000a; Abecasis et al., 2000b), with 22 traits examined. All alcohol-related quantitative traits were first transformed to normality using a piecewise normal transformation and were corrected for sex and age effects by fitting covariates in the regression model. Drug-related quantitative traits (i.e. pack years and quantitative cannabis use) were log-transformed, the effects of sex, age (linear and quadratic) and interactions between sex and age (linear and quadratic) were tested in a regression framework, significant covariates were regressed out and the resulting residuals were used for quantitative transmission disequilibrium tests. Three types of association tests were performed. An analysis robust to population stratification was conducted using the orthogonal “within” test in QTDT. Since parents were not genotyped this analysis only included families with two DZ offspring. To account for the fact that transmissions were not independent in the DZ families due to the presence of linkage in DZ pairs, a permutation procedure (10,000 permutations) was used to correct the p-values for the orthogonal test. Secondly, analyses of all 2618 families were
