GeneSet Information

Tier IV GS408332 • Molecular genetics of cocaine use disorders in humans

DESCRIPTION:

Heritability estimates for cocaine use disorder in humans are high and genetic risk factors for cocaine addiction have been investigated by candidate gene association studies (CGAS) and genome-wide association studies (GWAS)

LABEL:

Molecular genetics of cocaine use disorders in humans

SCORE TYPE:

P-Value

DATE ADDED:

2024-03-22

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Noèlia Fernàndez-Castillo, Judit Cabana-Domínguez, Roser Corominas, Bru Cormand

TITLE:

Molecular genetics of cocaine use disorders in humans.

JOURNAL:

Molecular psychiatry Jan 2022, Vol 27, pp. 624-639

ABSTRACT:

Drug addiction, one of the major health problems worldwide, is characterized by the loss of control in drug intake, craving, and withdrawal. At the individual level, drugs of abuse produce serious consequences on health and have a negative impact on the family environment and on interpersonal and work relationships. At a wider scale, they have significant socio-economic and public health consequences and they cause delinquency and citizen insecurity. Cocaine, a psychostimulant substance, is one of the most used illicit drugs, especially in America, Western Europe, and Australia. Cocaine use disorders (CUD) are complex multifactorial conditions driven by both genetic and environmental influences. Importantly, not all people who use cocaine develop CUD, and this is due, at least in part, to biological factors that are encoded in the genome of individuals. Acute and repeated use of cocaine induces epigenetic and gene expression changes responsible for the neuronal adaptations and the remodeling of brain circuits that lead to the transition from use to abuse or dependence. The purpose of this review is to delineate such factors, which should eventually help to understand the inter-individual variability in the susceptibility to cocaine addiction. Heritability estimates for CUD are high and genetic risk factors for cocaine addiction have been investigated by candidate gene association studies (CGAS) and genome-wide association studies (GWAS), reviewed here. Also, the high comorbidity that exists between CUD and several other psychiatric disorders is well known and includes phenotypes like schizophrenia, aggression, antisocial or risk-taking behaviors. Such comorbidities are associated with a worse lifetime trajectory, and here we report shared genetic factors that may contribute to them. Gene expression changes and epigenetic modifications induced by cocaine use and chronic abuse in humans are addressed by reviewing transcriptomic studies performed on neuronal cells and on postmortem brains. We report some genes which expression is altered by cocaine that also bear genetic risk variants for the disorder. Finally, we have a glance to the pharmacogenetics of CUD treatments, still in early stages. A better understanding of the genetic underpinnings of CUD will foster the search of effective treatments and help to move forward to personalized medicine. PUBMED: 34453125
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Annotation Information

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Brain (D001921)
Review (D016454)
Family (D005190)
Humans (D006801)
Comorbidity (D015897)
Street Drugs (D013287)
Environment (D004777)
Aggression (D000374)
Genome (D016678)
Comprehension (D032882)
Biological Factors (D001685)
Gene Expression (D015870)
Public Health (D011634)
Work (D014937)
Risk Factors (D012307)
Risk (D012306)
Risk-Taking (D012309)
Ursidae (D001503)
Health (D006262)
Phenotype (D010641)
Americas (D000569)
Europe (D005060)
Genes (D005796)
Cocaine (D003042)
Cells (D002477)
Lead (D007854)
Australia (D001315)
Medicine (D008511)
Schizophrenia (D012559)
Pharmacogenetics (D010597)
Association (D001244)
brain (MA:0000168)
addiction (MP:0002555)
aggressive behavior (GO:0002118)
gene expression (GO:0010467)
Humans (EDAM_topic:2815)
Genetics (EDAM_topic:3053)
Cell biology resources (EDAM_topic:2229)
Pharmacogenomics (EDAM_topic:0208)
Transcriptomics (EDAM_topic:0203)
Report (EDAM_data:2048)
Database search (EDAM_operation:2421)
lead atom (CHEBI:25016)
cocaine (CHEBI:27958)
cocaine(1+) (CHEBI:60056)
drug (CHEBI:23888)
lead(0) (CHEBI:27889)
Acute (HP:0011009)
Behavioral abnormality (HP:0000708)
Chronic (HP:0011010)
schizophrenia (DOID:5419)
disease (EFO:0000408)
individual (EFO:0000542)
risk factor (EFO:0003919)
aggressive behavior (EFO:0003015)
control (EFO:0001461)
cocaine dependence (EFO:0002610)
western blot assay (MMO:0000669)
scale (MMO:0000217)
scale (UBERON:0002542)
brain (UBERON:0000955)
adult cerebral ganglion (UBERON:6110636)
cud (UBERON:0012114)

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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