GeneSet Information

Tier III GS409038 • Differentially expressed genes in nucleus accumbens of human cases with alcohol depedency vs. control_pvalue

DESCRIPTION:

The complete differential gene expression geneset was made available at NCBI GEO (NAc accession no.: GSE62699) and obtained using the GEO2R tool. Gene expression was assayed using Affymetrix GeneChip Human Genome U133A 2.0 (HG-U133A 2.0) on 22,214 probe sets spanning ~ 18,400 mRNA transcripts, and the Affymetrix GeneChip miRNA 3.0 microarray interrogating the expression of 1733 mature miRNAs as previously described [24]. None of the mRNA or miRNA probes were excluded based on quality control criteria outlined in previous studies [18]. Raw probe data were GCRMA background corrected, log2 transformed, and quantile normalized using Partek Genomics Suite v6.23 (PGS; Partek Inc., St. Louis, MO) to obtain relative gene expression values. A principal component analysis was used to identify potential outlier samples. Only one case sample was removed from the analyses, leaving 18 controls and 17 cases (n = 35) for both brain regions. It has become widely accepted to verify a subset of microarray-generated gene expression changes via an independent platform such as qPCR. Considering limited tissue availability and our extensive use of the Affymetrix platform in the past, we did not include microarray validation in this study which is similar to what other groups have done in the past [25]. We have previously ‘validated’ the same array and platform in independent qPCR experiments with a concordance between microarray and qPCR platforms exceeding 80% in the past [18].

LABEL:

DEG NAc AD cases vs control_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

8861

DATE ADDED:

2024-09-03

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

Eric Vornholt, John Drake, Mohammed Mamdani, Gowon McMichael, Zachary N. Taylor, Silviu-Alin Bacanu, Michael F. Miles, Vladimir I. Vladimirov

TITLE:

Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC

JOURNAL:

PLoS One 12 20, Vol 15, pp. 1-19

ABSTRACT:

Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n = 35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc = 6; PFC = 3) and miRNA (NAc = 3; PFC = 2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc = 6; PFC = 4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA = 37, miRNA = 9; PFC: mRNA = 17, miRNA = 16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction. PUBMED: 33332381
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Annotation Information

No sequence read archive data associated with this GeneSet.


Executive Function (D056344)
Projection (D011385)
Genome, Human (D015894)
Principal Component Analysis (D025341)
Immunity (D007109)
Gene Regulatory Networks (D053263)
Biological Products (D001688)
Quantitative Trait Loci (D040641)
MicroRNAs (D035683)
Gene Expression (D015870)
RNA, Messenger (D012333)
Prefrontal Cortex (D017397)
Nucleus Accumbens (D009714)
Morphogenesis (D009024)
Genomics (D023281)
Alcohols (D000438)
Alcoholism (D000437)
accumbens nucleus (MA:0000892)
frontal association cortex (MA:0000906)
addiction (MP:0002555)
nascent polypeptide-associated complex (GO:0005854)
immune response (GO:0006955)
developmental process (GO:0032502)
localization (GO:0051179)
cell projection (GO:0042995)
anatomical structure morphogenesis (GO:0009653)
gene expression (GO:0010467)
cell morphogenesis (GO:0000902)
Pathway or network (EDAM_data:2600)
Transcriptomics (EDAM_topic:0203)
Functional and non-coding RNA (EDAM_topic:0659)
Nucleic acid features (SNP) (EDAM_data:2092)
Pathways, networks and models (EDAM_topic:0602)
Probes and primers (EDAM_topic:0632)
N-acetyl-L-cysteine (CHEBI:28939)
dilC18(5) dye (CHEBI:52027)
messenger RNA (CHEBI:33699)
perfluorinated compound (CHEBI:134091)
Alcoholism (HP:0030955)
alcohol abuse (DOID:1574)
alcohol dependence (DOID:0050741)
Mantle cell lymphoma (EFO:1001469)
obsolete_accumbens nucleus (EFO:0000906)
executive function (EFO:0007046)
real-time polymerase chain reaction (MMO:0000460)
high throughput transcription profiling by microarray (MMO:0000649)
prefrontal bone (UBERON:0010750)
neural nucleus (UBERON:0000125)
prefrontal cortex (UBERON:0000451)
nucleus incertus (UBERON:0035973)
nucleus accumbens (UBERON:0001882)
collection of eyelashes (UBERON:0010168)
anatomical projection (UBERON:0004529)
adult cerebral ganglion (UBERON:6110636)

Gene List • 12311 Genes

Genes in threshold: 8861

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