Psychological Medicine

Original Articles

Schizophrenia genetic variants are not associated with intelligence

A. F. Terwisscha van Scheltingaa1 c1, S. C. Bakkera1, N. E. M. van Harena1, E. M. Derksa2, J. E. Buizer-Voskampa1, W. Cahna1, S. Ripkea3  Psychiatric Genome-Wide Association Study (GWAS) Consortium, R. A. Ophoffa1a4 and R. S. Kahna1

a1 Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands

a2 Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands

a3 Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA

a4 Center for Neurobehavioral Genetics, University of California, Los Angeles, USA


Background 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.

Method 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.

Results 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 (R 2 = 0.055, p = 2.1 × 10−7) and with IQ in the entire sample (R 2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status.

Conclusions 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.

(Received October 15 2012)

(Revised January 07 2013)

(Accepted January 15 2013)

(Online publication February 15 2013)

Key words

  • Cognition;
  • deletion;
  • duplication;
  • endophenotype;
  • IQ;
  • polygenic;
  • SNP


c1 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:


  Members of the GWAS Consortium are listed in the Appendix.