While novel in its approach to integrating genetic and molecular data in postmortem alcohol research, our study is not without limitations. First, postmortem brain studies are observational, as the manipulation of the brain of living human subjects is not possible. Although the cross-sectional nature of these studies limits causal inferences, we believe our eQTL analysis, and subsequent integration with GWAS data, are major steps toward clarifying the directionality of these observations. Secondly, although our sample size (N = 36) is the largest postmortem alcohol study in the NAc to date, the sample size is still small. In an attempt to reduce the experimental variance and allow for increased power, we performed stringent case/ control matching for factors known to systemically impact gene expression levels, an approach that has been successfully applied before [85–88]. We believe that by using this experimental design and implementing integrative multivariate approaches, we can greatly further our understanding of the alcohol addiction processes and translate these advances into effective therapeutic strategies for patients suffering from substance use disorders.
