While there are undoubtedly numerous ways to score or weight genes, we have shown that this simple empirical approach is effective. Our results demonstrate the utility of gene ranking after cross-species data integration. Since this initial study demonstrated the utility of this approach, we are continuing to expand the number of data sets and improve the scoring scheme through a more sophisticated optimization of weighting parameters. As more data is included, additional alcohol GWAS results become available, and more sophisticated gene ranking algorithms are developed, we expect improvement in specificity and sensitivity. For example, there are many gene expression studies in rat brain from animals evaluated for alcohol-preference behavior [2,28-31], and they will be integrated in future gene ranking. However, our initial gene targeting experiments in animal models, using the ranked gene lists derived in this study, have already identified several novel genes that alter ethanol response behaviors in mice, Drosophila or C. elegans (unpublished data). This provides direct support of our cross-species gene ranking.
