Fuller Tova, Reus Victor
Deptartment of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco School of Medicine, San Francisco, CA, USA.
F1000Res. 2019 Sep 12;8. doi: 10.12688/f1000research.18130.1. eCollection 2019.
Until recently, advances in understanding the genetic architecture of psychiatric disorders have been impeded by a historic, and often mandated, commitment to the use of traditional, and unvalidated, categorical diagnoses in isolation as the relevant phenotype. Such studies typically required lengthy structured interviews to delineate differences in the character and duration of behavioral symptomatology amongst disorders that were thought to be etiologic, and they were often underpowered as a result. Increasing acceptance of the fact that co-morbidity in psychiatric disorders is the rule rather than the exception has led to alternative designs in which shared dimensional symptomatology is analyzed as a quantitative trait and to association analyses in which combined polygenic risk scores are computationally compared across multiple traditional categorical diagnoses to identify both distinct and unique genetic and environmental elements. Increasing evidence that most mental disorders share many common genetic risk variants and environmental risk modifiers suggests that the broad spectrum of psychiatric pathology represents the pleiotropic display of a more limited series of pathologic events in neuronal development than was originally believed, regulated by many common risk variants and a smaller number of rare ones.
直到最近，对精神疾病遗传结构的理解进展一直受到阻碍，这是由于长期以来（且常常是规定性地）一直致力于孤立地使用传统的、未经验证的分类诊断作为相关表型。此类研究通常需要冗长的结构化访谈，以描述被认为具有病因学意义的不同疾病之间行为症状学特征和持续时间的差异，结果往往样本量不足。越来越多的人认识到，精神疾病共病是常态而非例外，这导致了替代设计，即将共享的维度症状学作为定量性状进行分析，并进行关联分析，在关联分析中，通过计算比较多个传统分类诊断的综合多基因风险评分，以识别不同的和独特的遗传和环境因素。越来越多的证据表明，大多数精神障碍共享许多常见的遗传风险变异和环境风险调节因素，这表明比起最初认为的，广泛的精神病理谱代表了神经元发育中一系列更有限的病理事件的多效性表现，这些病理事件由许多常见风险变异和较少数量的罕见变异所调控。
