The impact of copy number deletions on general cognitive ability and ventricle size in patients with schizophrenia and healthy control subjects

Background: General cognitive ability is usually lower in individuals with schizophrenia, partly due to genetic influences. However, the specific genetic features related to general cognitive ability are poorly understood. Individual variation in a specific type of mutation, uncommon genetic deletions, has recently been linked with both general cognitive ability and risk for schizophrenia. Methods: We derived measures of the aggregate number of uncommon deletions (i.e., those occurring in 3% or less of our combined samples) and the total number of base pairs affected by these deletions in individuals with schizophrenia (n = 79) and healthy control subjects (n = 110) and related each measure to the first principal component of a large battery of cognitive tests, a common technique for characterizing general cognitive ability. These two measures of mutation load were also evaluated for relationships with total brain gray matter, white matter, and lateral ventricle volume. Results: The groups did not differ on genetic variables. Multivariate general linear models revealed a group (control subjects vs. patients)×uncommon deletion number interaction, such that the latter variable was associated with lower general cognitive ability and larger ventricles in patients but not control subjects. Conclusions: These data suggest that aggregate uncommon deletion burden moderates central features of the schizophrenia phenotype.