Alcohol Use Disorder Polygenic Score Compared With Family History and ADH1B

作者：Dongbing Lai, Michael Zhang, Marco Abreu, Tae‐Hwi Schwantes‐An, Grace Chan, Danielle M. Dick, Chella Kamarajan, Weipeng Kuang, John I. Nürnberger, Martin H. Plawecki, John P. Rice, Marc A. Schuckit, Bernice Porjesz, Yunlong Liu, Tatiana Foroud · 发表于：JAMA Network Open · 年份：2024 · DOI：10.1001/jamanetworkopen.2024.52705 · 被引用次数：7 · 研究领域：Genetic Associations and Epidemiology、Substance Abuse Treatment and Outcomes、Alcohol Consumption and Health Effects

Importance: Identification of individuals at high risk of alcohol use disorder (AUD) and subsequent application of prevention and intervention programs has been reported to decrease the incidence of AUD. The polygenic score (PGS), which measures an individual's genetic liability to a disease, can potentially be used to evaluate AUD risk. Objective: To assess the estimability and generalizability of the PGS, compared with family history and ADH1B, in evaluating the risk of AUD among populations of European ancestry. Design, Setting, and Participants: This genetic association study was conducted between October 1, 2023, and May 21, 2024. A 2-stage design was used. First, the pruning and thresholding method was used to calculate PGSs in the screening stage. Second, the estimability and generalizability of the best PGS was determined using 2 independent samples in the testing stage. Three cohorts ascertained to study AUD were used in the screening stage: the Collaborative Study on the Genetics of Alcoholism (COGA), the Study of Addiction: Genetics and Environment (SAGE), and the Australian Twin-Family Study of Alcohol Use Disorder (OZALC). The All of Us Research Program (AOU), which comprises participants with diverse backgrounds and conditions, and the Indiana Biobank (IB), consisting of Indiana University Health system patients, were used to test the best PGS. For the COGA, SAGE, and OZALC cohorts, cases with AUD were determined using Diagnostic and Statistical Manual of Mental...