The association between SYT1-rs2251214 and cocaine use disorder further supports its role in psychiatry.
Prog Neuropsychopharmacol Biol Psychiatry
; 94: 109642, 2019 08 30.
Article
em En
| MEDLINE
| ID: mdl-31059723
Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder and other externalizing phenotypes in adults with ADHD, as well as with response to methylphenidate (MPH) treatment. In this context, we sought to evaluate, in an independent sample, the association of this variant with CUD, a phenotype that shares common biological underpinnings with the previously associated traits. We tested the association between SYT1-rs2251214 and CUD susceptibility and severity (addiction severity index) in a sample composed by 315 patients addicted to smoked cocaine and 769 non-addicted volunteers. SYT1-rs2251214 was significantly associated with susceptibility to CUD, where the G allele presented increased risk for the disorder in the genetic models tested (Pâ¯=â¯0.0021, ORâ¯=â¯1.44, allelic; Pâ¯=â¯0.0012, ORâ¯=â¯1.48, additive; Pâ¯=â¯0.0127, ORâ¯=â¯1.41, dominant). This is the same allele that was associated with increased risk for ADHD and other externalizing behaviors, as well as poor response to MPH treatment in previous studies. These findings suggest that the neurotransmitter exocytosis pathway might play a critical role in the liability for psychiatric disorders, especially externalizing behaviors and CUD.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos Relacionados ao Uso de Cocaína
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Predisposição Genética para Doença
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Sinaptotagmina I
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Prog Neuropsychopharmacol Biol Psychiatry
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido