Despite several findings at the level of individual loci, genes and even gene-set terms (for EA), none of the biological units identified in this GWAS were related to genes previously linked to alcohol or drug related phenotypes. The gene sets, for instance, were broadly related to hemostasis and signal transduction. Prior gene set enrichment analyses have identified other gene sets related to signal transduction more broadly but not specifically via our gene-set terms66,67. However, as shown in Supplemental Figure S11, loci on chromosome 1, 3, 13 and 7, as well as the 4 genes that surpassed genome-wide correction (CRKL, DZIP3, SBK3, P2RX6) did show associations (p < 0.05) with other psychiatric, cognitive and behavioral traits. For instance, based on comparisons with other published and unpublished GWAS across multiple phenotypes, CRKL variants have been linked to age at smoking cessation (p=0.002) while DZIP3 variants have been related to bipolar disorder (p=3.3E-05). Nonetheless, the nature of the effect of these variants on alcohol and illicit drug dependence remains unknown.
