Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data

摘要: Genome-wide association studies on alcohol dependence, by themselves, have yet to account for the estimated heritability of disorder and provide incomplete mechanistic understanding this complex trait. Integrating brain ethanol-responsive gene expression networks from model organisms with human genetic data dependence could aid in identifying dependence-associated genes functional which they are involved. This study used a modification Edge-Weighted Dense Module Searching genome-wide (EW-dmGWAS) approach co-analyze whole-genome ethanol-exposed mouse tissue, protein-protein interaction databases dependence-related studies. Results revealed novel prefrontal cortex, nucleus accumbens, ventral tegmental area. Three these were overrepresented signals an independent dataset. These significantly ontology categories involving several mechanisms, including actin filament-based activity, transcript regulation, Wnt Syndecan-mediated signaling, ubiquitination. Together, insight mechanisms contributing dependence.