Predictive performance for alcohol use disorder of polygenic scores based on the general addiction risk factor and problematic alcohol use

IF 3.6 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-09-13 DOI:10.1016/j.drugalcdep.2025.112877

Ana M. Pérez-Gutiérrez , Gerardo Flórez , Vanessa Blanco , Fernando L. Vázquez , Enric Abellí-Deulofeu , Lluisa Ortega , Antonia Serrano , Francisco Arias , Francisco Navarrete , Francina Fonseca , Valentín Estévez , Jesús Gómez Trigo , Fernando Facal , Manuel Arrojo , Jorge Manzanares , Roberto Muga , Laia Miquel , Fernando Rodríguez de Fonseca , Marta Torrens , Gabriel Rubio , Javier Costas

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引用次数: 0

Abstract

Background

Polygenic scores (PGSs) may play a role in targeted prevention of alcohol use disorder (AUD) by risk stratification. A latent genetic factor representing common liability to different substance use disorders (SUDs), known as the addiction risk factor (AdRF), was recently characterized. Our aim was to analyze the predictive performance for AUD of the AdRF PGS, comparing it with PGSs of problematic alcohol use (PAU) and of a common liability factor to substance use involvement.

Methods

PGSs were estimated across two datasets, comprising 1637 treatment-seeking AUD patients and 4178 controls. Logistic regression was used to evaluate performance of ancestry-normalized PGSs. Subgroup sensitivity analyses were tested based on clinical data. Sex-dependent effects were assessed by comparing PGSs between sexes.

Results

Tail-based measures revealed a better performance of the AdRF PGS than the other PGSs. Compared with the remaining subjects, those at the top decile of PGS presented a 3.3-fold greater odds of AUD. Other analyses revealed similar performance of the AdRF and PAU PGSs. The effect estimates were larger in subgroups with addictive and psychiatric comorbidities, higher severity, and earlier age of onset. Women patients presented higher PAU and AdRF PGSs than men patients.

Conclusions

This new generation of PGSs is one step closer to precision public health for AUD prevention. Alcohol-specific genetic factors are not determinant for predicting AUD risk, which may benefit from shared genetic susceptibility among different SUDs. Our data suggest sex differences in genetic susceptibility, probably as a result of complex interplay between genes and social environment.

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基于一般成瘾风险因素和问题性酒精使用的多基因评分对酒精使用障碍的预测性能

背景多基因评分（pgs）可能通过风险分层在有针对性地预防酒精使用障碍（AUD）中发挥作用。一种潜在的遗传因素代表了对不同物质使用障碍（sud）的共同责任，被称为成瘾风险因素（AdRF），最近被表征。我们的目的是分析AdRF PGS对AUD的预测性能，并将其与问题酒精使用（PAU）和物质使用涉及的共同责任因素的PGS进行比较。方法在两个数据集中估计spgs，包括1637名寻求治疗的AUD患者和4178名对照组。使用逻辑回归来评估祖先归一化pgs的性能。根据临床资料进行亚组敏感性分析。通过比较两性间的pgs来评估性别依赖性效应。结果基于数据的测量显示AdRF PGS比其他PGS表现更好。与其他受试者相比，处于PGS前十分位数的受试者出现AUD的几率高出3.3倍。其他分析显示AdRF和PAU pgs的性能相似。在成瘾和精神合并症、严重程度较高和发病年龄较早的亚组中，效果估计更大。女性患者PAU和AdRF pgs均高于男性患者。新一代的pgs向精准预防AUD的公共卫生又迈进了一步。酒精特异性遗传因素不是预测AUD风险的决定性因素，这可能得益于不同sud之间共享的遗传易感性。我们的数据表明遗传易感性的性别差异，可能是基因和社会环境之间复杂相互作用的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.