A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives.

Autor:	Deng WQ; Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Ontario L8N 3K7, Canada.; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3K7, Canada., Belisario K; Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Ontario L8N 3K7, Canada.; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3K7, Canada., Gray JC; Department of Medical and Clinical Psychology, Uniformed Services University, Bethesda, MD 20814, United States., Levitt EE; Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Ontario L8N 3K7, Canada.; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3K7, Canada., MacKillop J; Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton, Hamilton, Ontario L8N 3K7, Canada.; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3K7, Canada.
Jazyk:	angličtina
Zdroj:	Alcohol and alcoholism (Oxford, Oxfordshire) [Alcohol Alcohol] 2024 Jan 17; Vol. 59 (2).
DOI:	10.1093/alcalc/agad093
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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