The frequency of alcohol dependence and comorbid nicotine and cocaine dependence is consistent with the study design and ascertainment protocols for each study (Table 1). Rs1229984 is strongly associated with alcohol dependence in each dataset (Table 3). See Supplementary Table 1 for results for the full models. In the meta-analysis across the three adult studies, which included 2298 alcohol dependent cases and 3334 non-dependent controls, the allele encoding His48 is significantly associated with reduced risk for alcohol dependence, with an odds ratio of 0.34 (95% CI 0.24, 0.48) and p value = 6.6 × 10−10. The magnitude of effect is similar in both European American and African American populations. Analyses were repeated using principal components to ensure that the association is not an artifact of population stratification, and results are essentially unchanged (Supplementary Table 2). The findings are robust, not only with respect to ethnicity, but also with major covariates (age, sex, nicotine and cocaine dependence), as removing or limiting covariates did not markedly affect the results (Supplementary Tables 3 and 4). These results are consistent with the recent meta-analysis