The SAGE sample is a case-control series selected from three large, complementary datasets: Collaborative Study on the Genetics of Alcoholism, Family Study of Cocaine Dependence, and Collaborative Genetics Study of Nicotine Dependence. After removing 129 individuals in SAGE who were also part of the 118 extended families in the primary analysis, data from 2647 subjects of European descent were used to replicate promising associations (p<0.0001) identified in the COGA sample. Detailed characteristics of this sample and the genotyping platform were described in Bierut et al.11. Imputed dosage data were obtained using the same method as described in supplementary information. The distribution of SC was similar to that of the COGA sample. We used PROC GLIMMIX in SAS to test the association of individual SNPs with SC including age, age-squared, gender, nicotine dependence, cocaine dependence, and pc1 as covariates. We used the GEE framework described above to analyze the association with AD.