Drug abuse cases were drawn from the UHS, one of the largest studies of street-recruited PWID in North America. Details on the study are provided in the Supplemental Information and elsewhere.(Kral et al., 2003) Briefly, eligibility criteria for study entry included injection of a drug in the past 30 days as verified by signs of venipuncture, ability to provide informed consent, age 18 or older, and ability to speak English or Spanish. Stored serum samples from UHS participants were selected for DNA extraction and genotyping on the Illumina Omni1-Quad BeadChip (see Supplemental Information). All of the genotyped UHS subjects were PWID but varied by reported drugs abused (Table 1). Past 30 day use of illicit drugs was assessed by self-report among the participating PWIDs, no confirmatory toxicology was performed. Most subjects were defined as heroin or other opioid abusers, who met the Office of National Drug Control Policy definition of heroin abuse by using 10 or more times in the past 30 days.(Morral et al., 2000; Rhodes et al., 2000) Other genotyped UHS subjects reported abuse (using 10 or more