GeneSet Information

Tier IV GS408361 • Transcriptome-wide association for cocaine self-administration in inbred and recombinant inbred mice

DESCRIPTION:

Gene expression associated with the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice. To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2 ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine. Data from Table S2 within the publication. Transcriptome-wide association studies for cocaine self-administration (related to Figure 6)

LABEL:

Transcriptome-wide association for cocaine self-administration in mice

SCORE TYPE:

Binary

DATE ADDED:

2024-03-26

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Arshad H Khan, Jared R Bagley, Nathan LaPierre, Carlos Gonzalez-Figueroa, Tadeo C Spencer, Mudra Choudhury, Xinshu Xiao, Eleazar Eskin, James D Jentsch, Desmond J Smith

TITLE:

Genetic pathways regulating the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice.

JOURNAL:

Cell reports Aug 2023, Vol 42, pp. 112856

ABSTRACT:

To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2 ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine. PUBMED: 37481717
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Population (D011153)
Behavior (D001519)
Genome-Wide Association Study (D055106)
RNA Editing (D017393)
Phenotype (D010641)
Cocaine (D003042)
Sprains and Strains (D013180)
Cannabinoids (D002186)
Association (D001244)
Receptors, Cannabinoid (D043882)
Publications (D011642)
addiction (MP:0002555)
regulation of alternative nuclear mRNA splicing, via spliceosome (GO:0000381)
alternative nuclear mRNA splicing, via spliceosome (GO:0000380)
RNA modification (GO:0009451)
response to cocaine (GO:0042220)
Map position (EDAM_data:2012)
Microarray data (EDAM_data:2603)
Pathways, networks and models (EDAM_topic:0602)
Genotype and phenotype (EDAM_topic:0625)
medroxyprogesterone acetate (CHEBI:6716)
cocaine(1+) (CHEBI:60056)
ribonucleic acid (CHEBI:33697)
cannabinoid (CHEBI:67194)
mean arterial pressure (EFO:0006340)
transcription profiling by high throughput sequencing (EFO:0002770)
RNA-seq assay (MMO:0000659)
adult cerebral ganglion (UBERON:6110636)

Gene List • 19 Genes

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