European American and African American cases were drawn from the UHS, one of the largest studies of street-recruited injection drugs users in North America (37). See the Supplement for further details on the UHS design. Stored serum samples from 3,227 UHS participants were selected for genotyping on the Illumina Omni1-Quad BeadChip. Over 60% of the genotyped UHS participants met the Office of National Drug Control Policy definition of heroin abuse (injecting 10+ times in the past 30 days) (38, 39), which is highly correlated with clinical levels of dependence on the Severity of Dependence Scale (40, 41) and with DSM-IV (42) heroin abuse/dependence in analyses of the National Household Survey on Drug Use and Health data (87% positive predictive value; see Table S1 and Supplemental Methods). These UHS participants, who abused heroin an average of 80.9 times in the past month and were very likely dependent on it, are henceforth referred to as heroin addiction cases. The remaining genotyped UHS participants, who were addicted to cocaine or other substances but not addicted to heroin, were not included in the current study.
