GeneSet Information

Tier IV GS408362 • Positional candidates for QTL associated with cocaine IVSA phenotypes_cis-eQTL p-value

DESCRIPTION:

Mice from 39 BXD strains acquired cocaine IVSA (0.56 mg/kg/infusion). Mice from 29 BXD strains completed a full dose-response curve (0.032-1.8 mg/kg/infusion). We identified independent genetic correlations between cocaine IVSA and measures of environmental exploration and cocaine sensitization. We identified genome-wide significant quantitative trait loci (QTL) on chromosomes 7 and 11 associated with shifts in the dose-response curve and on chromosome 16 associated with sessions to acquire cocaine IVSA. Using publicly available gene expression data from the nucleus accumbens, midbrain, and prefrontal cortex of drug-naïve mice, we identified Aplp1 and Cyfip2 as positional candidates underlying the behavioral QTL on chromosomes 7 and 11, respectively. A genome-wide significant trans-eQTL linking Fam53b (a GWAS candidate for human cocaine dependence) on chromosome 7 to the cocaine IVSA behavioral QTL on chromosome 11 was identified in the midbrain; Fam53b and Cyfip2 were co-expressed genome-wide significantly in the midbrain. Shown here are Priority positional candidates for behavioral QTL associated with cocaine IVSA phenotypes_cis-eQTL p-value

LABEL:

Positional candidates for QTL associated with cocaine IVSA phenotypes_cis-eQTL p-value

SCORE TYPE:

P-Value

DATE ADDED:

2024-03-26

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Price E Dickson, Mellessa M Miller, Michele A Calton, Jason A Bubier, Melloni N Cook, Daniel Goldowitz, Elissa J Chesler, Guy Mittleman

TITLE:

Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel.

JOURNAL:

Psychopharmacology Feb 2016, Vol 233, pp. 701-14

ABSTRACT:

Cocaine addiction is a major public health problem with a substantial genetic basis for which the biological mechanisms remain largely unknown. Systems genetics is a powerful method for discovering novel mechanisms underlying complex traits, and intravenous drug self-administration (IVSA) is the gold standard for assessing volitional drug use in preclinical studies. We have integrated these approaches to identify novel genes and networks underlying cocaine use in mice. PUBMED: 26581503
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Chromosomes, Human, Pair 7 (D002897)
Genetics (D005823)
Chromosomes (D002875)
Quantitative Trait Loci (D040641)
Gene Expression (D015870)
Public Health (D011634)
Chromosomes, Human, Pair 16 (D002885)
Chromosomes, Human, Pair 11 (D002880)
Prefrontal Cortex (D017397)
Phenotype (D010641)
Nucleus Accumbens (D009714)
Cocaine (D003042)
Sprains and Strains (D013180)
accumbens nucleus (MA:0000892)
frontal association cortex (MA:0000906)
addiction (MP:0002555)
sensitization (GO:0046960)
chromosome (GO:0005694)
gene expression (GO:0010467)
Microarray data (EDAM_data:2603)
Transcriptomics (EDAM_topic:0203)
Pathways, networks and models (EDAM_topic:0602)
gold atom (CHEBI:29287)
cocaine(1+) (CHEBI:60056)
glyoxal-lysine dimer (CHEBI:59965)
atomic nucleus (CHEBI:33252)
cocaine dependence (DOID:9975)
milligram per kilogram (EFO:0002902)
obsolete_accumbens nucleus (EFO:0000906)
cocaine dependence (EFO:0002610)
prefrontal bone (UBERON:0010750)
central sulcus of insula (UBERON:0035925)
neural nucleus (UBERON:0000125)
prefrontal cortex (UBERON:0000451)
nucleus accumbens (UBERON:0001882)

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