Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Nat Rev Genet. 2021 Nov;22(11):712-729. doi: 10.1038/s41576-021-00377-1. Epub 2021 Jul 1.
Substance use disorders (SUDs) are conditions in which the use of legal or illegal substances, such as nicotine, alcohol or opioids, results in clinical and functional impairment. SUDs and, more generally, substance use are genetically complex traits that are enormously costly on an individual and societal basis. The past few years have seen remarkable progress in our understanding of the genetics, and therefore the biology, of substance use and abuse. Various studies - including of well-defined phenotypes in deeply phenotyped samples, as well as broadly defined phenotypes in meta-analysis and biobank samples - have revealed multiple risk loci for these common traits. A key emerging insight from this work establishes a biological and genetic distinction between quantity and/or frequency measures of substance use (which may involve low levels of use without dependence), versus symptoms related to physical dependence.
物质使用障碍(SUD)是指使用合法或非法物质(如尼古丁、酒精或阿片类药物)导致临床和功能障碍的疾病。SUD 以及更广泛的物质使用是遗传复杂的特征,从个人和社会层面来看代价巨大。在过去的几年中,我们对物质使用和滥用的遗传学,因此也是生物学的理解取得了显著的进展。各种研究——包括在深度表型样本中对明确定义的表型,以及在荟萃分析和生物库样本中对广泛定义的表型——揭示了这些常见特征的多个风险位点。这项工作的一个关键新见解是,在物质使用的数量和/或频率(可能涉及没有依赖的低水平使用)与与身体依赖相关的症状之间建立了生物学和遗传学上的区分。