Fifth, we did not take into account the tissue specificity of regulatory markers when delineating DHS SNPs, as all variants located in (or in perfect LD with) a DHS site in any of the RoadMap tissue lines was considered a DHS SNP. Therefore, SNPs that have only a regulatory function in tissues that are not relevant to alcohol use would have been included in the DHS-scores along with true important functional variants, diluting the magnitude of the per-SNP association and the difference in association between SNPs included in the DHS versus non-DHS scores. We performed supplementary analyses using scores that included DHS SNPs limited to brain tissue samples and DHS SNPs present in two or more tissue samples to determine whether SNPs from certain samples were more relevant. Neither of these scores at either p-value threshold predicted ADsx. This may be due to the very small number of markers included in both the brain tissue score (p<.01 = 139; p<.05 = 653) or the two tissue score (p<.01 = 495; p<.05 = 2,571).
