Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability.
Drug Alcohol Depend
; 256: 111058, 2024 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-38244365
ABSTRACT
BACKGROUND:
Opioid use disorder (OUD), a serious health burden worldwide, is associated with lower cognitive function. Recent studies have demonstrated a negative genetic correlation between OUD and general cognitive ability (COG), indicating a shared genetic basis. However, the specific genetic variants involved, and the underlying molecular mechanisms remain poorly understood. Here, we aimed to quantify and identify the genetic basis underlying OUD and COG.METHODS:
We quantified the extent of genetic overlap between OUD and COG using a bivariate causal mixture model (MiXeR) and identified specific genetic loci applying conditional/conjunctional FDR. Finally, we investigated biological function and expression of implicated genes using available resources.RESULTS:
We estimated that ~94% of OUD variants (4.8k out of 5.1k variants) also influence COG. We identified three novel OUD risk loci and one locus shared between OUD and COG. Loci identified implicated biological substrates in the basal ganglia.CONCLUSION:
We provide new insights into the complex genetic risk architecture of OUD and its genetic relationship with COG.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
/
8_ODS3_consumo_sustancias_psicoactivas
Problema de saúde:
2_sustancias_psicoativas
/
8_opioid_abuse
Assunto principal:
Estudo de Associação Genômica Ampla
/
Transtornos Relacionados ao Uso de Opioides
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Drug Alcohol Depend
Ano de publicação:
2024
Tipo de documento:
Article