Hovatta Iiris, Barlow Carrolee
Research Program of Molecular Neurology, Biomedicum, University of Helsinki, Finland.
Ann Med. 2008;40(2):92-109. doi: 10.1080/07853890701747096.
Human anxiety disorders represent one of the most common mental illnesses. They are complex diseases with both genetic and environmental factors affecting their predisposition. Since the basic neuronal mechanisms are shared across mammalian species, the same set of genes may regulate critical aspects of anxiety in humans and in lower species. In this review, we first summarize findings from human molecular genetic approaches to anxiety disorders or anxiety-related personality traits: genome-wide scans and candidate gene studies in large families or case-control cohorts. We then discuss recent studies that have used genome-wide methods in mouse strains to identify genes that regulate anxiety-like behavior. Although it has been difficult to pinpoint specific susceptibility genes for anxiety disorders, ongoing efforts to collect larger study cohorts and to develop new genetic tools should help in this task. Studies in animals have shown that novel quantitative trait locus (QTL) and functional genomics approaches might lead to the identification of regulators of anxiety in mice, and that these genes can be tested for their involvement in human anxiety disorders. Finally, breakthroughs are expected in the fine-mapping of human and mouse genetic linkage regions and in the identification of novel candidate genes using genome-wide methods in mouse models of anxiety.
人类焦虑症是最常见的精神疾病之一。它们是复杂的疾病，遗传和环境因素都会影响其易感性。由于基本的神经元机制在哺乳动物物种中是共有的，同一组基因可能会调节人类和低等物种焦虑的关键方面。在这篇综述中，我们首先总结人类分子遗传学方法对焦虑症或焦虑相关人格特质的研究结果：全基因组扫描以及在大家族或病例对照队列中的候选基因研究。然后，我们讨论最近在小鼠品系中使用全基因组方法来识别调节焦虑样行为基因的研究。尽管很难确定焦虑症的特定易感基因，但持续努力收集更大的研究队列并开发新的遗传工具应该有助于完成这项任务。动物研究表明，新的数量性状基因座（QTL）和功能基因组学方法可能会导致在小鼠中识别出焦虑调节因子，并且可以测试这些基因是否参与人类焦虑症。最后，预计在人类和小鼠遗传连锁区域的精细定位以及使用全基因组方法在焦虑小鼠模型中识别新的候选基因方面会取得突破。
