By integrating miRNA and mRNA co-expression modules, we were able to examine the regulatory roles that miRNA have on their gene targets (as both mRNA and miRNA data was generated from the same subjects). Performing a module eigengene (ME) correlation analysis, we found that the significant miRNA and mRNA AD modules were also negatively correlated with each other,i.e.miRNA modules upregulated in chronic alcoholics were negatively correlated with the downregulated mRNA modules and vice versa—suggesting that the neuropathology of AD is at least partially modulated by specific miRNA:mRNA interactions. Interestingly, we also observed positively correlated miRNA and mRNA modules that contained miRNA:mRNA targeting pairs. Although these interactions were not further assessed, they may be important for disease development. Considering the canonical role of miRNA in negatively modulating gene expression, these results are surprising. Similar observations were also reported in an animal based study, where highly significant positive miRNA:mRNA correlations were detected in the PFC of mice undergoing acute alcohol exposure [22]. One potential explanation is that the positive miRNA:mRNA expression correlations observed in the animal model are the result of an
