This study has several limitations. First, we stratified by ethnicity and sex, which reduced sample sizes and affected the power of our analysis. Nonetheless, the significant associations revealed in African-origin men are consistent with the notion that men may be socially more prone to environmental influences that promote substance use and thus more vulnerable to addiction [46]. Second, for SNP rs2377339, we observed heterogeneous genetic effects, suggesting interactions between race, sex, and the gene, because the association is much weakened after adjusting for race and gender. Such interactions have been suggested in other addiction research [44, 45, 47]. Again, our result further supports the importance to examine interactions among genes, race, and sex in addiction.
