Transcriptome organization for chronic alcohol abuse in human brain
Open accessAbstract
Alcohol dependence is a heterogeneous psychiatric disorder characterized by high genetic heritability and neuroadaptations occurring from repeated drug exposure. Through an integrated systems approach we observed consistent differences in transcriptome organization within postmortem human brain tissue associated with the lifetime consumption of alcohol. Molecular networks, determined using high-throughput RNA sequencing, for drinking behavior were dominated by neurophysiological targets and signaling mechanisms of alcohol. The systematic structure of gene sets demonstrates a novel alliance of multiple ion channels, and related processes, underlying lifetime alcohol consumption. Coordinate expression of these transcripts was enriched for genome-wide association signals in alcohol dependence and a meta-analysis of alcohol self-administration in mice. Further dissection of genes within alcohol consumption networks revealed the potential interaction of alternatively spliced transcripts. For example, expression of a human-specific isoform of the voltage-gated sodium channel subunit SCN4B was significantly correlated to lifetime alcohol consumption. Overall, our work demonstrates novel convergent evidence for biological networks related to excessive alcohol consumption, which may prove fundamentally important in the development of pharmacotherapies for alcohol dependence.
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Alcohol exposure triggers changes in gene expression and biological pathways in human brain.
“Alcohol exposure triggers changes in gene expression and biological pathways in human brain.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [9]
Transcriptomes from complex tissues such as human brain may be organized into networks of co-expressed genes that better reflect the biological functions and organization of the tissue.
“Transcriptomes from complex tissues, such as human brain, may be organized into networks of co-expressed genes that better reflect the biological functions and organization of the tissue7–14.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [9]
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Self-citationGenome- and transcriptome-wide splicing associations with alcohol use disorder
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A Pathway-Based Genomic Approach to Identify Medications: Application to Alcohol Use Disorder
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- Authors
- Farris, S. P., Arasappan, D., Hunicke-Smith, S., Harris, R. A., & Mayfield, R. D.
- Affiliations
- The University of Texas at Austin (US)
- Corresponding author
- Mayfield, R D
- Venue
- Molecular Psychiatry
- Published
- 2014-12-02
- Volume
- 20
- Issue
- 11
- Pages
- 1438-1447
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4452464
- OpenAlex
- W2052338190
- Cited by
- 111
- References
- 76
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 6
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Texas at Austin
- University of Sydney
- National Health and Medical Research Council
- National Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism (AA013517, AA020926, P01AA020683, U01AA013517, AA019382, RC2AA019382, R24AA012725, U24AA013517, AA007471, AA012404, R28AA012725, R01AA012404, T32AA007471, U01AA020926)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- chronic alcohol abuse, alcoholism, postmortem brain, gene co-expression network, ion channels, SCN4B, voltage-gated sodium channels, alternative splicing, alcohol self-administration, neural adaptation, alcohol consumption
- MeSH terms
- Alcohol Drinking, Alcoholism, Animals, Brain, Chronic Disease, Humans, Postmortem Changes, Computational Biology, Gene Expression Profiling, Mice, Gene Regulatory Networks, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Transcriptome, Voltage-Gated Sodium Channel beta-4 Subunit
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