An interaction-based model for neuropsychiatric features of copy-number variants

Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features.

可变表达性拷贝数变异（copy-number variants，CNVs）的典型特征为其所关联的神经精神表型呈现广泛的表型异质性。目前，针对此类表型，通过在单个CNV区域内定位单一致病基因的研究策略尚未获得成功。本研究提出，结合致病性评估指标、模式生物功能实验与基因表达数据等多维度证据，可推断每个CNV区域内的多个基因共同参与了所观测到的表型发生。我们进一步提出，各区域内的候选基因或可通过共通通路相互作用，协同调控单个基因的表型效应，这一论点凸显了CNV关联神经精神特征的遗传复杂性。