Lastly, this study delved beyond the allelic architecture of alcoholism, searching for wider biological patterns among alleles of varying association strengths by means of permuted gene enrichment analysis. Of the ontologies and signaling pathways that show significant enrichment in our data set, four are particularly compelling, as they represent broad signals (i.e., significance across three or more GWAS P-value thresholds) and are shared by both EAs and AAs: a) Maf transcription factors, which regulate cell differentiation and potentially brain segmentation (Cordes & Barsh 1994; Sadl et al. 2003); b) Hox AbdB genes, a family of transcription factors involved in embryogenesis and axial patterning; c) chloride transport, which plays a crucial role in synaptic inhibition through the activity of GABA and glycine neurotransmitters; and d) glycine and serine metabolism, for which glycine is an important inhibitory neurotransmitter. When their empirical P-values from the enrichment analyses are plotted, they reveal remarkably similar trends between the two populations (Fig. 4), with overlapping peaks, significant correlations (r ranging from 0.73 to 0.44), and non-significant Kolmogorov-Smirnov (K–S) distances between the P-value distributions. All of this,
