COMT gene features relative to amplicons interrogated for methylation. COMT spans ~32 kb (chromosome 22q11.21, human build NCBI 37/hg 19, bp 19925733 – 19957832), with two major transcript variants encoding soluble and membrane bound (S-COMT and MB-COMT) enzyme forms, respectively (drawn to scale). 13 amplicons (001–013, orange arrows), were designed to interrogate methylation in CpG islands (blue cylinders) throughout COMT. Previously identified SNPs associated with impulsivity or pain sensitivity are listed by rs number (red font), with approximate SNP position indicated by blue vertical arrows. Top row: The S-COMT variant is encoded by four exons (black lined white boxes), regulated by promoter P1 (green bar), and possibly by a predicted promoter (PP) 5’ of P1. Bottom Row: The MB-COMT is encoded by 6 exons (with multiple possible variants of exon 1 (1-v1, 1-v2, 1-v3). Expanded view (dashed diagonal lines), highlight three ~40 bp repeat sequence motifs that we identified spanning ~1.5 kb beginning in exon 1-v2 through intron 1; the ATG1 and ATG2 translational start sites (TSS) in Exon 3 for S-COMT and MB-COMT, respectively; and the rs4680 SNP in Exon 4 encoding the substitution of valine (val) with methionine (met) at codon 158.