Tawa Elisabeth A, Hall Samuel D, Lohoff Falk W
Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
Alcohol Alcohol. 2016 Sep;51(5):507-14. doi: 10.1093/alcalc/agw046. Epub 2016 Jul 21.
Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article.
In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS).
Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown.
Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD.
This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH.
酒精使用障碍（AUD）是一种慢性精神疾病，其特征是有害的饮酒模式会导致负面的情绪、身体和社会影响。虽然对AUD的潜在病理生理学了解甚少，但有大量证据表明存在遗传因素；然而，识别AUD的普遍遗传风险变异一直很困难。本文将综述近期寻找AUD易感基因的研究进展。
在本综述中，我们概述了关于AUD的遗传研究，包括双生子研究、连锁研究、候选基因研究和全基因组关联研究（GWAS）。
已确定了几个AUD的潜在遗传易感因素，但发现酒精代谢基因乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）对AUD的发生具有保护作用。GWAS还确定了一系列与AUD和酒精相关表型相关的单核苷酸多态性（SNP），强调了该疾病的复杂性和异质性。此外，与酒精代谢基因相比，这些发现中的许多效应大小较小，且生物学相关性往往未知。
尽管多种方法的研究表明AUD存在遗传基础，但识别遗传风险变异具有挑战性。GWAS研究正在取得一些有希望的结果；然而，需要更大的样本量来改善GWAS结果和分辨率。随着遗传学领域的快速发展，全基因组测序可能很快成为探究导致AUD复杂表型基因和神经生物学途径的新标准。
本综述探讨了酒精使用障碍（AUD）的遗传基础，重点是用于识别遗传风险变异的GWAS方法。与AUD和酒精相关表型相关的最有希望的结果包括酒精代谢基因ADH和ALDH的SNP。
