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Schizophrenia genetic variants are not associated with intelligence

  • A. F. Terwisscha van Scheltinga (a1), S. C. Bakker (a1), N. E. M. van Haren (a1), E. M. Derks (a2), J. E. Buizer-Voskamp (a1), W. Cahn (a1), S. Ripke (a3), R. A. Ophoff (a1) (a4) and R. S. Kahn (a1)
  • DOI:
  • Published online: 15 February 2013

Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence.


IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls.


Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2 = 0.055, p = 2.1 × 10−7) and with IQ in the entire sample (R2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status.


Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.

Corresponding author
*Address for correspondence: A. F. Terwisscha van Scheltinga, M.D. Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Huispostnummer A00.241, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. (Email:
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Psychological Medicine
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