When looking at the individual SNPs, it is likely that we did not find loci associated with heroin dependence at genome-wide significance due to our relatively small sample size. Whether the genes identified in our study can be considered to have any pathophysiological role in heroin abuse depends on replication of these results and future functional studies. Our limited replication assessment using summary data from a large GWAS in opioid dependence showed no evidence of replication at the SNP level. Similarly, when we looked at some of the common candidate genes [62–73], our results did not show significant association with any of these genes (Table C(i) and (ii) in S2 File). Nonetheless, among the SNP-based and gene-based results, there are individual genes implicated in addiction. ARHGEF10 has been discussed above, and GRIN3B (glutamate receptor, ionotropic, N-methyl-D-aspartate 3B) has been shown to be differentially expressed in heroin addicts compared to controls and methadone-maintained addicts [74], and was suggestively associated in gene-based analysis (p = 0.003; top SNP p = 0.6.8−5).
