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

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 hum...

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Autores principales: Mignogna, Kristin M., Bacanu, Silviu A., Riley, Brien P., Wolen, Aaron R., Miles, Michael F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481773/
https://www.ncbi.nlm.nih.gov/pubmed/31017905
http://dx.doi.org/10.1371/journal.pone.0202063
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author Mignogna, Kristin M.
Bacanu, Silviu A.
Riley, Brien P.
Wolen, Aaron R.
Miles, Michael F.
author_facet Mignogna, Kristin M.
Bacanu, Silviu A.
Riley, Brien P.
Wolen, Aaron R.
Miles, Michael F.
author_sort Mignogna, Kristin M.
collection PubMed
description 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.
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spelling pubmed-64817732019-05-07 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 R. Miles, Michael F. PLoS One Research Article 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. Public Library of Science 2019-04-24 /pmc/articles/PMC6481773/ /pubmed/31017905 http://dx.doi.org/10.1371/journal.pone.0202063 Text en © 2019 Mignogna et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mignogna, Kristin M.
Bacanu, Silviu A.
Riley, Brien P.
Wolen, Aaron R.
Miles, Michael F.
Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title_full Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title_fullStr Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title_full_unstemmed Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title_short Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data
title_sort cross-species alcohol dependence-associated gene networks: co-analysis of mouse brain gene expression and human genome-wide association data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481773/
https://www.ncbi.nlm.nih.gov/pubmed/31017905
http://dx.doi.org/10.1371/journal.pone.0202063
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