Lastly, laterality differences were apparent following multiple testing correction (i.e., rs75168521 genotype was associated with blunted right, but not left, VS response while rs1890881 genotype was associated with blunted left, but not right VS response in AA). While prior reports have found evidence of lateralized associations with reward-related processing in the VS76,77, the directionality of associations in our study were consistent across hemispheres and in some cases reached nominal levels of significance (Table 5). As such, it is possible that our lateralized findings resulted from limited power. Overall, our neuroimaging findings, while preliminary, showed ancestral specificity consistent with the GWAS, and suggest a putative role for the ANYDEP-associated variants in general reward responsiveness. However, despite correction for multiple testing, it is also plausible that these findings represent a false positive given our small sample, which also prevented us from testing potential quadratic effects which might be expected given that both relatively reduced and heightened VS response to reward were associated with genetic risk for substance use phenotypes.
