We further investigated the role of three DISC1 RVs in the initiation of opioid use and the development of OD in AAs. First, we tested the association between the RVs and opioid initiation, and no significant association was observed (P=0.1686). Then, we restricted the analysis to AAs who had initiated an opioid (n=1701), and found a significant association between the three RVs and OD (P=0.0041). rs139667828 had the strongest protective effect (P=0.0013). Its minor allele existed in 18 of the 1514 chromosomes (1.19%) in OD controls, and 5 of the 1832 chromosomes (0.27%) in OD cases.