Cross-species alcohol dependence-associated gene networks

Co-analysis of mouse brain gene expression and human genome-wide association data

Kristin M. Mignogna, Silviu A. Bacanu, Brien P. Riley, Aaron Wolen, Michael F. Miles

Research output: Contribution to journalArticle

Abstract

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-responsive 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.

Original languageEnglish (US)
Article numbere0202063
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Gene Regulatory Networks
Human Genome
alcohol abuse
Gene expression
Alcoholism
Brain
Genes
Alcohols
Genome-Wide Association Study
brain
Gene Expression
gene expression
genome
mice
Ethanol
ethanol
Syndecans
Genome
Protein Databases
Ventral Tegmental Area

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cross-species alcohol dependence-associated gene networks : Co-analysis of mouse brain gene expression and human genome-wide association data. / Mignogna, Kristin M.; Bacanu, Silviu A.; Riley, Brien P.; Wolen, Aaron; Miles, Michael F.

In: PloS one, Vol. 14, No. 4, e0202063, 01.04.2019.

Research output: Contribution to journalArticle

Mignogna, Kristin M. ; Bacanu, Silviu A. ; Riley, Brien P. ; Wolen, Aaron ; Miles, Michael F. / Cross-species alcohol dependence-associated gene networks : Co-analysis of mouse brain gene expression and human genome-wide association data. In: PloS one. 2019 ; Vol. 14, No. 4.
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