Copy number variation and neuropsychiatric illness

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.

Automated summary

Copy number variants (CNVs) at specific loci have been identified as important risk factors for several neuropsychiatric disorders, with pleiotropic effects and associations with cognitive impairment and other medical morbidities. While most neuropsychiatric CNVs are multigenic, gene-set analyses have implicated specific genes related to neuropsychiatric disorders. Future whole-genome sequencing studies have the potential to identify novel single-gene CNV associations, providing insights into the pathophysiology underlying these disorders.