Genome-wide association studies enrichment analysis (Table 2 and Supplementary Table 5) of all annotated genes from the OUD-associated differential mCpHs identified enrichment for two opioid gene sets—Methadone dose in opioid dependence (p-value = 3.00E-03; SORCS1, GRK5, E2F7, SPRY2, TRIB2, and BCL11A), and Opioid dependence (p-value = 6.18E-03; CNIH3, TACC2). The gene discussed is SPRY2; the disease is opiate dependence.