“…This problem is exaggerated when large-scale (e.g., genome-wide) explorations are conducted, since the number of false positive findings is greatly increased. However, by focusing on interactions between genes known to be involved in disease-related biological processes, one can maximize a priori biological plausibility and post-hoc interpretability while reducing the multiple testing correction threshold and computational burden (Pattin and Moore 2008). In this study, we investigated genes from the AD pathway of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which is a collection of manually curated pathways based on published literature for metabolism, genetic and environmental information processing, and human diseases, including AD (Kanehisa and Goto 2000; Kanehisa et al 2012).…”