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, as well as substantial sharing between annotated gene lists at peak enrichment thresholds (Table S7), suggest commonalities in the genetic mechanisms responsible for AD liability that transcend population differences in the underlying allelic architectures. For Maf transcription factors and AbdB genes, the strongest signals for enrichment occur at small GWAS P-values (< 0.10), indicating large to modest effects on AD risk by genes belonging to these particular groups, whereas chloride transport (which includes GABA receptors that have been often implicated in AD) and glycine/serine metabolism reveal peaks at markedly higher thresholds (< 0.60), pointing to more subtle effects that are likely to escape detection in most single marker association tests. These enrichment differences may represent molecular signatures of a hierarchical etiology, in which the effects of the Maf and AbdB transcription factors on developmental and pathophysiological pathways related to AD are more proximate to the disease endpoint than chloride transport and glycine-related neurochemical systems. (Gaino & Fishell 2002; Pandey 2004;
