All subjects selected for the GWAS met criteria for DSM-IV OD. Subjects who had been treated with methadone were asked the following question: “When you were taking methadone, what was your usual dosage?” Data on daily methadone dose were available for a total of 383 AAs and 1,027 EAs. Phenotype data were prepared for GWAS using the R statistical computing environment,33 which was also used to generate phenotype data summary statistics (means, standard deviations). Methadone dose data, in milligrams (mg), were transformed to normality with an inverse-normal transformation,34 and used as the dependent variable in the GWAS. As previously described, imputation of genotype data was performed from the 1000 Genomes Project Phase 1 reference panel using Impute2.35–37 The GWAS was carried out with Plink v1.0738, adjusting for age, sex, weight, and 10 principal components (PCs). Within each of the two ancestry groups (EA and AA), separate analyses were run on subjects genotyped on the HumanOmni1-Quadv1.0 and Human Core Exome microarrays. SNPs were filtered out if the minor allele frequency (MAF) was <5%, or if the imputation INFO score was <0.7.
