Two recent GWAS are of particular relevance, one because of the larger sample size and the additional analyses for risk pathways [13], while the second one used exposed and non-exposed controls [14]. Gelernter et al [13] performed a well-designed study utilizing an initial discovery sample of 5697 individuals, followed by two replication stages: stage 1, N = 4063 participants; stage 2, N = 2549 participants, all satisfying the criteria for opioid dependence. The increase in sample size was sufficient to produce results that were replicated across the different phases and interestingly, that were functionally relevant to the phenotype. Association analyses produced population-specific variants for the analyses using case-control status, symptom count and meta-analyzed results of all three phases. The African-American sample yielded the most significant results with variants in KCNG2 (potassium voltage-gate channel modifier subfamily G member 2). Subsequent pathway analyses captured the role of subthreshold results to reveal two potentially functional pathways, calcium signaling and synaptic long term potentiation. Neurotransmitter signaling plays a key role in drug dependence [3,15]; CAMK2B (calcium/calmodulin dependent protein kinase II beta) was shown to
