University of Missouri-Columbia and the Midwest Alcoholism Research Center, Columbia, MO 65211, USA.
Addict Biol. 2010 Apr;15(2):200-16. doi: 10.1111/j.1369-1600.2009.00189.x.
This review article discusses the importance of identifying gene-environment interactions for understanding the etiology and course of alcohol use disorders and related conditions. A number of critical challenges are discussed, including the fact that there is no organizing typology for classifying different types of environmental exposures, many key human environmental risk factors for alcohol dependence have no clear equivalents in other species, much of the genetic variance of alcohol dependence in human is not 'alcohol specific', and the potential range of gene-environment interactions that could be considered is so vast that maintaining statistical control of Type 1 errors is a daunting task. Despite these and other challenges, there appears to be a number of promising approaches that could be taken in order to achieve consilience and ecologically valid translation between human alcohol dependence and animal models. Foremost among these is to distinguish environmental exposures that are thought to have enduring effects on alcohol use motivation (and self-regulation) from situational environmental exposures that facilitate the expression of such motivations but do not, by themselves, have enduring effects. In order to enhance consilience, various domains of human approach motivation should be considered so that relevant environmental exposures can be sampled, as well as the appropriate species to study them in (i.e. where such motivations are ecologically relevant). Foremost among these are social environments, which are central to the initiation and escalation of human alcohol consumption. The value of twin studies, human laboratory studies and pharmacogenetic studies is also highlighted.
这篇综述文章讨论了识别基因-环境相互作用对于理解酒精使用障碍及相关疾病的病因和病程的重要性。文中讨论了一些关键的挑战,包括:没有用于分类不同类型环境暴露的组织分类法;许多关键的人类环境风险因素在其他物种中没有明确的对应物;人类酒精依赖症的遗传方差大部分不是“酒精特异性”的;可以考虑的基因-环境相互作用的潜在范围非常广泛,以至于要保持第一类错误的统计控制是一项艰巨的任务。尽管存在这些和其他挑战,但似乎有一些有前途的方法可以用来实现人类酒精依赖症和动物模型之间的一致性和生态有效性转化。其中最重要的是区分那些被认为对酒精使用动机(和自我调节)有持久影响的环境暴露,以及那些促进这种动机表达但本身没有持久影响的情境环境暴露。为了增强一致性,应该考虑人类趋近动机的各个领域,以便能够对相关的环境暴露进行采样,以及研究它们的适当物种(即这些动机在生态上是相关的)。其中最重要的是社会环境,它是人类饮酒行为的开始和升级的核心。还强调了双胞胎研究、人类实验室研究和药物遗传学研究的价值。