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Anxiety genetics – findings from cross-species genome-wide approaches

机译：焦虑遗传学–跨物种全基因组方法的发现

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摘要

Anxiety disorders are complex diseases, which often occur in combination with major depression, alcohol use disorder, or general medical conditions. Anxiety disorders were the most common mental disorders within the EU states in 2010 with 14% prevalence. Anxiety disorders are triggered by environmental factors in genetically susceptible individuals, and therefore genetic research offers a great route to unravel molecular basis of these diseases. As anxiety is an evolutionarily conserved response, mouse models can be used to carry out genome-wide searches for specific genes in a setting that controls for the environmental factors. In this review, we discuss translational approaches that aim to bridge results from unbiased genome-wide screens using mouse models to anxiety disorders in humans. Several methods, such as quantitative trait locus mapping, gene expression profiling, and proteomics, have been used in various mouse models of anxiety to identify genes that regulate anxiety or play a role in maintaining pathological anxiety. We first discuss briefly the evolutionary background of anxiety, which justifies cross-species approaches. We then describe how several genes have been identified through genome-wide methods in mouse models and subsequently investigated in human anxiety disorder samples as candidate genes. These studies have led to the identification of completely novel biological pathways that regulate anxiety in mice and humans, and that can be further investigated as targets for therapy.
机译：焦虑症是复杂的疾病，通常与严重的抑郁症，饮酒障碍或一般医疗状况共同发生。焦虑症是2010年欧盟各州中最常见的精神障碍，患病率为14％。遗传易感人群中的环境因素引发了焦虑症，因此基因研究为揭示这些疾病的分子基础提供了一条绝好的途径。由于焦虑是进化上保守的反应，因此可以使用小鼠模型在控制环境因素的环境中对特定基因进行全基因组搜索。在这篇综述中，我们讨论了旨在将使用小鼠模型进行无偏见的全基因组筛选结果与人类焦虑症联系起来的翻译方法。多种方法，例如定量性状基因座作图，基因表达谱分析和蛋白质组学，已用于各种焦虑症小鼠模型中，以鉴定调节焦虑症或在维持病理性焦虑症中起作用的基因。我们首先简要讨论焦虑的进化背景，这证明了跨物种方法的合理性。然后，我们描述如何通过全基因组方法在小鼠模型中鉴定出几个基因，然后在人类焦虑症样本中作为候选基因进行研究。这些研究导致了对调节小鼠和人类焦虑的全新生物途径的鉴定，并且可以作为治疗的靶点进行进一步研究。

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