Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Neurosci. 2018 Dec;21(12):1656-1669. doi: 10.1038/s41593-018-0275-1. Epub 2018 Nov 26.
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10) and African ancestries (rs2066702; P = 2.2 × 10). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
酒精依赖症（AD）的发病具有遗传性，但目前人们对其复杂的多基因结构或与其他疾病的遗传关系知之甚少。为了发现与 AD 相关的基因座，并阐明 AD 与其他精神和行为障碍之间的关系，我们进行了迄今为止最大规模的 AD 与 DSM-IV 诊断的全基因组关联研究。对来自 28 项病例对照和基于家族的研究的 14904 名 AD 患者和 37944 名对照者进行了全基因组数据分析，按遗传背景（欧洲裔，n=46568；非洲裔，n=6280）进行分层。在欧洲裔（rs1229984；P=9.8×10）和非洲裔（rs2066702；P=2.2×10）中，鉴定出不同 ADH1B 变体的独立、全基因组显著效应。观察到与 17 种表型存在显著的遗传相关性，包括精神分裂症、注意缺陷多动障碍、抑郁症以及香烟和大麻的使用。AD 的遗传基础与饮酒行为的遗传基础仅部分重叠，这突出了病理性和非病理性饮酒行为之间的遗传差异。
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