A subset of the patients meeting the above inclusion criteria had previously been consented for genomic study and genotyped (on either the Illumina Human-Hap550 or Illumina Human610-Quad microarray) by the Center for Applied Genomics at CHOP, as approved by the CHOP IRB. Sample details and quality control of phenotype and genotype data have been described previously.41 The 1000 Genomes Project reference panel and Impute2 35–37 were used to impute the top methadone dose GWAS SNP. In this morphine-treated sample, we analyzed total intravenous morphine dose (μg/kg) as a quantitative trait, and used SNPTEST V242 to evaluate the methadone dose GWAS-identified SNP. We used the same statistical model previously developed for this sample, which included age, body mass index, and American Society of Anesthesiologists physical status as covariates.41