GeneSet Information

Tier III GS409288 • long non-coding RNA (lncRNA) expressed in nucleus accumbens (Nac) affected by eQTLs at FDR p<0.10 and associated with alcohol dependence (AD)

DESCRIPTION:

LncRNA and protein-coding gene (PCG) expressions in the NAc from 41 subjects with alcohol dependence (AD) and 41 controls were assessed via a regression model. Weighted gene coexpression network analysis was used to identify lncRNA and PCG networks (i.e., modules) significantly correlated with AD. Within the significant modules, key network genes (i.e., hubs) were also identified. The lncRNA and PCG hubs were correlated via Pearson correlations to elucidate the potential biological functions of lncRNA. The lncRNA and PCG hubs were further integrated with GWAS data to identify expression quantitative trait loci (eQTL). Integration of hubs with genotype data identified 243 eQTLs affecting the expression of 39 and 204 PCG and lncRNA hubs, respectively. Data shown here are lncRNA hub "genes" that were associated with/ affected by eQTLs at FDR p<0.10.

LABEL:

lncRNA eQTL associations in subjects with AD, FDR p<0.10

SCORE TYPE:

Binary

DATE ADDED:

2024-10-31

DATE UPDATED:

2025-07-21

SPECIES:

AUTHORS:

John Drake, Gowon O McMichael, Eric Sean Vornholt, Kellen Cresswell, Vernell Williamson, Chris Chatzinakos, Mohammed Mamdani, Siddharth Hariharan, Kenneth S Kendler, Gursharan Kalsi, Brien P Riley, Mikhail Dozmorov, Michael F Miles, Silviu-Alin Bacanu, Vladimir I Vladimirov

TITLE:

Assessing the Role of Long Noncoding RNA in Nucleus Accumbens in Subjects With Alcohol Dependence.

JOURNAL:

Alcoholism, clinical and experimental research Dec 2020, Vol 44, pp. 2468-2480

ABSTRACT:

Background: Long noncoding RNA (lncRNA) have been implicated in the etiology of alcohol use. Since lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step toward understanding lncRNA functions in alcohol use and addiction. Thus, we sought to profile lncRNA expression in the nucleus accumbens (NAc) in a large postmortem alcohol brain sample. Methods: LncRNA and protein-coding gene (PCG) expressions in the NAc from 41 subjects with alcohol dependence (AD) and 41 controls were assessed via a regression model. Weighted gene coexpression network analysis was used to identify lncRNA and PCG networks (i.e., modules) significantly correlated with AD. Within the significant modules, key network genes (i.e., hubs) were also identified. The lncRNA and PCG hubs were correlated via Pearson correlations to elucidate the potential biological functions of lncRNA. The lncRNA and PCG hubs were further integrated with GWAS data to identify expression quantitative trait loci (eQTL). Results: At Bonferroni adj. p-value ≤ 0.05, we identified 19 lncRNA and 5 PCG significant modules, which were enriched for neuronal and immune-related processes. In these modules, we further identified 86 and 315 PCG and lncRNA hubs, respectively. At false discovery rate (FDR) of 10%, the correlation analyses between the lncRNA and PCG hubs revealed 3,125 positive and 1,860 negative correlations. Integration of hubs with genotype data identified 243 eQTLs affecting the expression of 39 and 204 PCG and lncRNA hubs, respectively. Conclusions: Our study identified lncRNA and gene networks significantly associated with AD in the NAc, coordinated lncRNA and mRNA coexpression changes, highlighting potentially regulatory functions for the lncRNA, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PUBMED: 33067813
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Annotation Information

No sequence read archive data associated with this GeneSet.


Brain (D001921)
Clinical Coding (D059019)
RNA (D012313)
RNA, Untranslated (D022661)
Gene Regulatory Networks (D053263)
Biological Products (D001688)
Quantitative Trait Loci (D040641)
RNA, Messenger (D012333)
Proteins (D011506)
Genotype (D005838)
Nucleus Accumbens (D009714)
Alcoholism (D000437)
accumbens nucleus (MA:0000892)
brain (MA:0000168)
addiction (MP:0002555)
nascent polypeptide-associated complex (GO:0005854)
RNA (EDAM_topic:0099)
Genetics (EDAM_topic:3053)
Pathway or network (EDAM_data:2600)
protein (EDAM_format:1208)
Transcriptomics (EDAM_topic:0203)
Functional and non-coding RNA (EDAM_topic:0659)
Pathways, networks and models (EDAM_topic:0602)
rna (EDAM_format:1213)
Genotype and phenotype (EDAM_topic:0625)
N-acetyl-L-cysteine (CHEBI:28939)
protein (CHEBI:36080)
benzylpenicillin (CHEBI:18208)
NAC (CHEBI:7421)
ethanol (CHEBI:16236)
protein polypeptide chain (CHEBI:16541)
alcohol (CHEBI:30879)
ribonucleic acid (CHEBI:33697)
messenger RNA (CHEBI:33699)
alcohol dependence (DOID:0050741)
obsolete_accumbens nucleus (EFO:0000906)
genotype (EFO:0000513)
brain (UBERON:0000955)
central sulcus of insula (UBERON:0035925)
nervous system cell part layer (UBERON:0022303)
nucleus accumbens (UBERON:0001882)
anatomical projection (UBERON:0004529)
adult cerebral ganglion (UBERON:6110636)
cell layer (UBERON:0000119)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

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