A review of the cognitive impact of neurodevelopmental and neuropsychiatric associated copy number variants

The heritability of intelligence or general cognitive ability is estimated at 41% and 66% in children and adults respectively. Many rare copy number variants are associated with neurodevelopmental and neuropsychiatric conditions (ND-CNV), including schizophrenia and autism spectrum disorders, and may contribute to the observed variability in cognitive ability. Here, we reviewed studies of intelligence quotient or cognitive function in ND-CNV carriers, from both general population and clinical cohorts, to understand the cognitive impact of ND-CNV in both contexts and identify potential genotype-specific cognitive phenotypes. We reviewed aggregate studies of sets ND-CNV broadly linked to neurodevelopmental and neuropsychiatric conditions, and genotype-first studies of a subset of 12 ND-CNV robustly associated with schizophrenia and autism. Cognitive impacts were observed across ND-CNV in both general population and clinical cohorts, with reports of phenotypic heterogeneity. Evidence for ND-CNV-specific impacts were limited by a small number of studies and samples sizes. A comprehensive understanding of the cognitive impact of ND-CNVs would be clinically informative and could identify potential educational needs for ND-CNV carriers. This could improve genetic counselling for families impacted by ND-CNV, and clinical outcomes for those with complex needs.

Automated summary

The heritability of intelligence or general cognitive ability is estimated to be 41% and 66% in children and adults, respectively. Rare copy number variants (ND-CNV) are associated with neurodevelopmental and neuropsychiatric conditions and can contribute to the variability in cognitive ability. This review examines the impact of ND-CNV on intelligence and cognitive function in both general population and clinical cohorts, and identifies genotype-specific cognitive phenotypes. The findings show that ND-CNV have cognitive impacts across different populations, but more studies and larger sample sizes are needed to determine ND-CNV-specific effects.