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Schizophrenia genetic variants are not associated with intelligence

Published online by Cambridge University Press:  15 February 2013

A. F. Terwisscha van Scheltinga ,
S. C. Bakker ,
N. E. M. van Haren ,
E. M. Derks ,
J. E. Buizer-Voskamp ,
W. Cahn ,
S. Ripke ,
R. A. Ophoff  and
R. S. Kahn
A. F. Terwisscha van Scheltinga*
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
S. C. Bakker
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
N. E. M. van Haren
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
E. M. Derks
Affiliation:
Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands
J. E. Buizer-Voskamp
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
W. Cahn
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
S. Ripke
Affiliation:
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
R. A. Ophoff
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands Center for Neurobehavioral Genetics, University of California, Los Angeles, USA
R. S. Kahn
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
*
*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: aterwiss@umcutrecht.nl)
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Abstract

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 (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.

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.

Keywords

CognitiondeletionduplicationendophenotypeIQpolygenicSNP
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 12 , December 2013 , pp. 2563 - 2570
Copyright
Copyright © Cambridge University Press 2013 

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