Salvatore Jessica E, Gottesman Irving I, Dick Danielle M
Department of Psychiatry, Virginia Commonwealth University, PO Box 980126, Richmond, VA 23298-0126.
Department of Psychology, University of Minnesota, N231 Elliott Hall, 75 East River Road, Minneapolis, MN 55455.
Curr Addict Rep. 2015 Mar;2(1):76-90. doi: 10.1007/s40429-015-0046-y.
The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches to AUD endophenotypes have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically-influenced pathways toward AUD.
内表型概念最初是作为一种策略提出的,旨在在精神疾病的基因识别研究中使用(据称)遗传上更简单的表型,它与密切相关的中间表型概念不同。在酒精使用障碍(AUD)研究领域,两种候选内表型已产生可重复的遗传关联:对酒精的反应水平和神经生理学标志物(如事件相关振荡和事件相关电位)。来自认知、感觉和神经影像学文献的其他候选内表型显示出前景,尽管需要更多证据来全面评估它们的潜在效用。对AUD内表型的转化方法有助于表征AUD内表型的潜在神经生物学和遗传学,并确定相关的药物干预措施。未来利用内表型的多基因性质并强调可能随发育而变化的内表型的研究,将提高这一概念在理解AUD的遗传影响途径方面的有用性。