Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
| Autor: | Aaron R. Wolen, Kristin M. Mignogna, Brien P. Riley, Silviu Alin Bacanu, Michael F. Miles |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Science ved/biology.organism_classification_rank.species Gene regulatory network Genome-wide association study Computational biology Biology Mice 03 medical and health sciences 0302 clinical medicine Species Specificity Gene expression medicine Animals Humans Gene Regulatory Networks Databases Protein Model organism Gene 030304 developmental biology Genetic association 0303 health sciences Multidisciplinary Ethanol ved/biology Alcohol dependence Brain Ventral tegmental area Alcoholism 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Medicine Human genome 030217 neurology & neurosurgery Genome-Wide Association Study Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 4, p e0202063 (2019) |
| ISSN: | 1932-6203 |
| Popis: | Genome-wide association studies on alcohol dependence, by themselves, have yet to account for the estimated heritability of the disorder and provide incomplete mechanistic understanding of this complex trait. Integrating brain ethanol-responsive gene expression networks from model organisms with human genetic data on alcohol dependence could aid in identifying dependence-associated genes and functional networks in which they are involved. This study used a modification of the Edge-Weighted Dense Module Searching for genome-wide association studies (EW-dmGWAS) approach to co-analyze whole-genome gene expression data from ethanol-exposed mouse brain tissue, human protein-protein interaction databases and alcohol dependence-related genome-wide association studies. Results revealed novel ethanol-regulated and alcohol dependence-associated gene networks in prefrontal cortex, nucleus accumbens, and ventral tegmental area. Three of these networks were overrepresented with genome-wide association signals from an independent dataset. These networks were significantly overrepresented for gene ontology categories involving several mechanisms, including actin filament-based activity, transcript regulation, Wnt and Syndecan-mediated signaling, and ubiquitination. Together, these studies provide novel insight for brain mechanisms contributing to alcohol dependence. |
| Databáze: | OpenAIRE |
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