MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Curr Opin Genet Dev. 2021 Jun;68:57-63. doi: 10.1016/j.gde.2021.02.014. Epub 2021 Mar 19.
Copy number variants (CNVs) at specific loci have been identified as important risk factors for several neuropsychiatric disorders, such as schizophrenia, autism spectrum disorder, intellectual disability (ID) and depression. These CNVs are individually rare (<0.5% frequency), have high effect sizes, and show pleiotropic effects for multiple neuropsychiatric disorders, which implies a shared aetiology. Neuropsychiatric CNVs are also associated with cognitive impairment and other medical morbidities, such as heart defects and obesity. As most neuropsychiatric CNVs are multigenic, it has been challenging to map their effects onto specific biological processes, although gene-set analyses have implicated genes related to the synapse and chromatin regulation. However, future whole-genome sequencing studies have potential for identifying novel single-gene CNV associations, which could provide insights into the pathophysiology underlying neuropsychiatric disorders.
特定位置的拷贝数变异 (CNVs) 已被确定为多种神经精神疾病的重要风险因素，如精神分裂症、自闭症谱系障碍、智力障碍 (ID) 和抑郁症。这些 CNVs 个体罕见（频率<0.5%），具有高效应大小，并对多种神经精神疾病表现出多效性，这意味着存在共同的发病机制。神经精神 CNVs 也与认知障碍和其他医学疾病相关，如心脏缺陷和肥胖。由于大多数神经精神 CNVs 是多基因的，因此将其影响映射到特定的生物学过程一直具有挑战性，尽管基因集分析已经涉及与突触和染色质调节相关的基因。然而，未来的全基因组测序研究有可能识别新的单基因 CNV 关联，这可能为神经精神疾病的病理生理学提供见解。
