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

Ronald A. Yeo, Steven W. Gangestad, Jingyu Liu, Stefan Ehrlich, Robert J. Thoma, Jessica Pommy, Andrew R. Mayer, S. Charles Schulz, Thomas H. Wassink, Eric M. Morrow, Juan R. Bustillo, Scott R. Sponheim, Beng Choon Ho, Vince D. Calhoun

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)540-545
Number of pages6
JournalBiological psychiatry
Issue number6
StatePublished - Mar 15 2013

Bibliographical note

Funding Information:
This research was supported by grants from the Department of Energy under Award Number DE-FG02-08ER64581 and the National Institute Health (Grants 5P20RR021938, 1RC1MH089257, and R01EB005846).

Funding Information:
SE is currently affiliated with the University Hospital Carl Gustav Carus Dresden, University of Technology, Dresden, Germany. Dr. Schulz reports grants from the National Institutes of Mental Health, Astra-Zeneca, Otsuka, and Myrida/RBM and consultations for Eli-Lilly and Genetech. All other authors report no biomedical financial interests or potential conflicts of interest.


  • Cognition
  • copy number variations
  • intelligence
  • mutations
  • schizophrenia
  • ventricles


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