Kos et al. (2013), using pathway analysis, aimed to identify specific ontologies and/or pathways (defined by ResNet Mammalian, Ariadne Genomics) that were enriched among the groups of SNPs identified in their risk profile scoring analyses in the COGA discovery and SAGE target samples. For each bin (n=20, defined by GWAS P-value threshold), they retained SNPs with consistent directions of effect in the discovery and target samples, assigned them to their corresponding genes, and evaluated the significance of enrichment via permutation. Although the majority of ontologies and pathways showed no enrichment, four ontologies displayed significant enrichment in the gene sets from both EAs and AAs. The pathways identified as enriched among the GWAS associations [Maf transcription factors, homeotic (Hox) AbdB genes, chloride transport, and glycine and serine metabolism] relate to brain development and inhibitory neurotransmission and may represent future targets for AD research.
