A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives.
Alcohol Alcohol
; 59(2)2024 Jan 17.
Article
em En
| MEDLINE
| ID: mdl-38261344
ABSTRACT
AIMS:
This study uses a high-resolution phenome-wide approach to evaluate the motivational mechanisms of polygenic risk scores (PRSs) that have been robustly associated with coarse alcohol phenotypes in large-scale studies.METHODS:
In a community-based sample of 1534 Europeans, we examined genome-wide PRSs for the Alcohol Use Disorders Identification Test (AUDIT), drinks per week, alcohol use disorder (AUD), problematic alcohol use (PAU), and general addiction, in relation to 42 curated phenotypes. The curated phenotypes were in seven categories alcohol consumption, alcohol reinforcing value, drinking motives, other addictive behaviors, commonly comorbid psychiatric syndromes, impulsivity, and personality traits.RESULTS:
The PRS for each alcohol phenotype was validated via its within-sample association with the corresponding phenotype (adjusted R2s = 0.35-1.68%, Ps = 0.012-3.6 × 10-7) with the exception of AUD. All PRSs were positively associated with alcohol reinforcing value and drinking motives, with the strongest effects from AUDIT-consumption (adjusted R2s = 0.45-1.33%, Ps = 0.006-3.6 × 10-5) and drinks per week PRSs (adjusted R2s = 0.52-2.28%, Ps = 0.004-6.6 × 10-9). Furthermore, the PAU and drinks per week PRSs were positively associated with adverse childhood experiences (adjusted R2s = 0.6-0.7%, Ps = 0.0001-4.8 × 10-4).CONCLUSIONS:
These results implicate alcohol reinforcing value and drinking motives as genetically-influenced mechanisms using PRSs for the first time. The findings also highlight the value of dissecting genetic influence on alcohol involvement through diverse phenotypic risk pathways but also the need for future studies with both phenotypic richness and larger samples.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Comportamento Aditivo
/
Alcoolismo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Alcohol Alcohol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá