from chemical dependency treatment units in the greater St. Louis metropolitan area along with community-based control subjects matched on several criteria such as age and race. The COGEND is a community-based case-control family study that recruited nicotine dependent cases and non-dependent smoking controls from the cities of Detroit and St. Louis. The current analyses focused on a subset of 2596 (COGA N = 957, FSCD N = 541, COGEND N = 1098) unrelated participants (44% male, mean age = 38.58 years, standard deviation = 9.80) of European descent (confirmed via principal component analysis including HAPMAP CEPH, Yoruban, Han Chineese, and Japanese samples as ancestral reference groups) drawn from all three studies that comprise SAGE. SAGE was selected for this study because it is the largest cohort of complementary datasets that is publicly available (additional description of SAGE is available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1). While the ascertainment strategy of each study focuses on a particular substance, the fact that substance users have a tendency to become involved with multiple substances allows for sampling of both single and multiple drug users, thereby increasing our power to examine the latent trait that is vulnerability to substance addiction (Supplemental Table S1 provides a description of rates
