For comparison with the UHS heroin addiction cases, we used six study cohorts from the database of Genotypes and Phenotypes (dbGaP) as a source of controls. Several prior studies have been reliably conducted using a similar design with study cases and population controls (43-48). See Table S2, Figure S2, and the Supplemental Methods for an outline of our cohort selection and quality control processes. There were no apparent biases underlying our control dataset, as indicated by genomic control inflation factor (λgc) <1.05 for all pair-wise combinations of dbGaP cohorts (Tables S3 and S4). Our final analysis dataset included 7,095 European Americans (711 UHS heroin addiction cases and 6,384 population controls) and 3,662 African Americans (1,293 UHS heroin addiction cases and 2,369 population controls).