Division of Behavioral Genetics, Department of Psychiatry at Rhode Island Hospital, USA.
Drug Alcohol Depend. 2012 Oct 1;125(3):179-91. doi: 10.1016/j.drugalcdep.2012.07.005. Epub 2012 Jul 31.
Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent upon our ability to identify patterns of genetic and environmental effects that influence a person's risk. Unfortunately, array-based whole genome investigations into heritable factors that explain why one person becomes dependent upon alcohol and another does not, have indicated that alcohol's genetic architecture is highly complex. That said, uncovering and interpreting the missing heritability in alcohol genetics research has become all the more important, especially since the problem may extend to our inability to model the cumulative and combinatorial relationships between common and rare genetic variants. As numerous studies begin to illustrate the dependency of alcohol pharmacotherapies on an individual's genotype, the field is further challenged to identify new ways to transcend agnostic genomewide association approaches. We discuss insights from genetic studies of alcohol related diseases, as well as issues surrounding alcohol's genetic complexity and etiological heterogeneity. Finally, we describe the need for innovative systems-based approaches (systems genetics) that can provide additional statistical power that can enhance future gene-finding strategies and help to identify heretofore-unrealized mechanisms that may provide new targets for prevention/treatments efforts. Emerging evidence from early studies suggest that systems genetics has the potential to organize our neurological, pharmacological, and genetic understanding of alcohol dependence into a biologically plausible framework that represents how perturbations across evolutionarily robust biological systems determine susceptibility to alcohol dependence.
针对精神病理，尤其是酒精成瘾的个性化治疗高度依赖于我们识别影响个体风险的遗传和环境效应模式的能力。不幸的是，基于阵列的全基因组研究表明，解释为什么有些人依赖酒精而另一些人不依赖酒精的遗传因素非常复杂。也就是说，揭示和解释酒精遗传学研究中的遗传缺失变得尤为重要，尤其是因为这个问题可能延伸到我们无法模拟常见和罕见遗传变异之间的累积和组合关系。随着越来越多的研究开始表明个体基因型对酒精药物治疗的依赖性，该领域进一步面临挑战，需要寻找新的方法来超越基于全基因组关联的盲目方法。我们讨论了酒精相关疾病的遗传学研究的见解，以及与酒精遗传复杂性和病因异质性相关的问题。最后，我们描述了需要创新的基于系统的方法（系统遗传学），该方法可以提供额外的统计能力，增强未来的基因发现策略，并有助于识别迄今为止尚未实现的机制，这些机制可能为预防/治疗工作提供新的靶点。早期研究的新兴证据表明，系统遗传学有可能将我们对酒精依赖的神经生物学、药理学和遗传学理解组织成一个有生物学意义的框架，代表了跨越进化稳健的生物系统的干扰如何决定对酒精依赖的易感性。
