Differential effect of deletions and duplications on general intelligence and social responsiveness
Deleterious deletions and duplications (copy number variations, CNVs) are identified in up to 11% of individuals referred to neurodevelopmental pediatric clinics. However, only few recurrent CNVs have been formally associated with neurodevelopmental disorders because the majority are too rare to perform individual association studies. We recently developed a new framework to estimate the effect size of undocumented CNVs on non-verbal intelligence quotient (NVIQ) and sought to extend this approach to another score measuring autistic traits.  We identified CNVs in an autism sample from the Simons Simplex Collection (SSC) and MSSNG, in their first-degree relatives, in a neurodevelopmental cohort and in individuals from an unselected population. Statistical models integrating scores of the genes encompassed in the CNVs were used to explain their effect on general intelligence and on social responsiveness.  Deletions and duplications decreased NVIQ and the effect of duplications was three-fold smaller than deletions. There was also a differential effect on social responsiveness: the ratio of the impairment conferred by deletions and duplications was 2:1 and this effect was mainly driven by NVIQ. Models estimates for general intelligence and social responsiveness were consistent with previously published observations. Our models, trained on CNVs encompassing >4,500 genes, suggest highly polygenic properties of CNVs with respect to cognition and social responsiveness. These models will help interpreting CNVs identified in the clinic.
SRS Copy-number variants General intelligence IQ Social responsiveness Autism Statistical models Genetic scores