The pathway analysis results are noteworthy primarily because they implicate variation in systems regulating calcium signaling. Although there were no individually GWS findings in calcium-system genes, calcium signaling was one of two primary domains implicated in our recent opioid dependence GWAS (the other was potassium signaling). There is prior association evidence of calcium system genes in cocaine dependence (e.g., neuronal calcium sensor 1, NCS1).29 Our results approaching GWS in the discovery Phase 1 sample obtained with SNPs near KCNT2 and SCLT1 suggest a possible link between CD and potassium signaling. Although the evidence of overlap in risk loci for opioid and cocaine dependence is limited, it is consistent with the high rate of comorbidity of these two disorders.
