Schizophrenia genetic variants are not associated with intelligence

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  • A.F.T. Van Scheltinga, University Medical Center Utrecht
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  • S.C. Bakker, University Medical Center Utrecht
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  • N.E.M. Van Haren, University Medical Center Utrecht
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  • E.M. Derks, University of Amsterdam
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  • J.E. Buizer-Voskamp, University Medical Center Utrecht
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  • W. Cahn, University Medical Center Utrecht
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  • S. Ripke, Massachusetts General Hospital
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  • R.A. Ophoff, University Medical Center Utrecht
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  • R.S. Kahn, University Medical Center Utrecht
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  • S. Ripke
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  • A.R. Sanders
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  • K.S. Kendler
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  • D.F. Levinson
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  • P. Sklar
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  • P.A. Holmans
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  • D.-Y. Lin
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  • J. Duan
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  • R.A. Ophoff
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  • O.A. Andreassen
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  • E. Scolnick
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  • S. Cichon
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  • D. St Clair
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  • A. Corvin
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  • H. Gurling
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  • Thomas Werge, Kobenhavns Universitet, Psychiatric Centre Sct. Hans, Copenhagen, Denmark
  • D. Rujescu
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  • D.H.R. Blackwood
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  • C.N. Pato
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  • A.K. Malhotra
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  • S. Purcell
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  • F. Dudbridge
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  • B.M. Neale
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  • L. Rossin
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  • P.M. Visscher
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  • D. Posthuma
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  • D.M. Ruderfer
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  • A. Fanous
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  • H. Stefansson
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  • S. Steinberg
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  • B.J. Mowry
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  • V. Golimbet
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  • M. De Hert
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  • E.G. Jönsson
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  • I. Bitter
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  • O.P.H. Pietiläinen
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  • D.A. Collier
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  • S. Tosato
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  • I. Agartz
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  • M. Albus
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  • M. Alexander
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  • R.L. Amdur
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  • Farooq Amin, Denmark
  • N. Bass
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  • S.E. Bergen
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  • D.W. Black
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  • A.D. Børglum, Denmark
  • M.A. Brown
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  • R. Bruggeman
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  • N.G. Buccola
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  • W.F. Byerley
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  • W. Cahn
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  • Rita M. Cantor, Denmark
  • V.J. Carr
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  • S.V. Catts
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  • K. Choudhury
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  • C.R. Cloninger
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  • P. Cormican
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  • N. Craddock
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  • P.A. Danoy
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  • Suvra Datta, Department of Biochemistry and Nutrition, Denmark
  • L. De Haan
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  • Ditte Demontis
  • D. Dikeos
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  • S. Djurovic
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  • P. Donnelly
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  • G. Donohoe
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  • Linh Thi Thuy Duong, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Copenhagen, Denmark
  • S. Dwyer
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  • Anders Fink-Jensen, Københavns Universitet, Department of Neuroscience and Pharmacology, Copenhagen, Denmark
  • R. Freedman
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  • N.B. Freimer
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  • M. Friedl
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  • L. Georgieva
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  • I. Giegling
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  • M. Gill
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  • Birte Yding Glenthøj, Copenhagen University Hospital, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen, Denmark
  • S. Godard
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  • M. Hamshere
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  • M. Hansen
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  • T. Hansen
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  • A.M. Hartmann
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  • F.A. Henskens
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  • D.M. Hougaard
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  • C.M. Hultman
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  • Andrés Ingason, National Institute for Health and Welfare - THL, Public Health Genomics Unit, Helsinki, Finland
  • A.V. Jablensky
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  • K.D. Jakobsen
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  • M. Jay
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  • G. Jürgens
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  • R.S. Kahn
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  • M.C. Keller
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  • G. Kenis
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  • E. Kenny
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  • Y. Kim
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  • G.K. Kirov
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  • H. Konnerth
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  • B. Konte
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  • L. Krabbendam
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  • R. Krasucki
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  • V.K. Lasseter
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  • C. Laurent
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  • J. Lawrence
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  • T. Lencz
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  • F.B. Lerer
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  • K.-Y. Liang
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  • P. Lichtenstein
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  • J.A. Lieberman
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  • D.H. Linszen
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  • J. Lönnqvist
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  • C.M. Loughland
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  • A.W. Maclean
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  • B.S. Maher
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  • W. Maier
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  • J. Mallet
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  • P. Malloy
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  • Manuel Mattheisen
  • M. Mattingsdal
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  • K.A. McGhee
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  • J.J. McGrath
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  • A. McIntosh
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  • D.E. McLean
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  • A. McQuillin
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  • I. Melle
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  • P.T. Michie
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  • V. Milanova
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  • D.W. Morris
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  • Ole Mors
  • Preben Bo Mortensen
  • V. Moskvina
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  • P. Muglia
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  • I. Myin-Germeys
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  • D.A. Nertney
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  • G. Nestadt
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  • J. Nielsen
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  • I. Nikolov
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  • Merete Nordentoft, Copenhagen University Hospital, Psychiatric Research Unit, Copenhagen, Denmark
  • N. Norton
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  • M.M. Nöthen
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  • C.T. O'Dushlaine
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  • A. Olincy
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  • L. Olsen
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  • F.A. O'Neill
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  • T.F. Ørntoft
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  • M.J. Owen
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  • C. Pantelis
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  • G. Papadimitriou
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  • M.T. Pato
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  • L. Peltonen
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  • H. Petursson
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  • B. Pickard
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  • J. Pimm
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  • A.E. Pulver
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  • V. Puri
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  • D. Quested
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  • E.M. Quinn
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  • Henrik Berg Rasmussen, Copenhagen University Hospital, Psychiatric Research Unit, Copenhagen, Denmark
  • J.M. Réthelyi
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  • R. Ribble
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  • M. Rietschel
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  • B.P. Riley
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  • M. Ruggeri
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  • U. Schall
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  • T.G. Schulze
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  • S.G. Schwab
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  • R.J. Scott
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  • J. Shi
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  • Engilbert Sigurdsson, University of Iceland, School of Medicine, Reykjavik, Iceland
  • J.M. Silverman
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  • C.C.A. Spencer
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  • K. Stefansson
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  • A. Strange
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  • E. Strengman
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  • T.S. Stroup
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  • J. Suvisaari
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  • Lars T. Terenius, Karolinska Institutet, Department of Clinical Neurosciences, Stockholm, Sweden
  • S. Thirumalai
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  • J.H. Thygesen
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  • S. Timm
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  • D. Toncheva
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  • E. Van Den Oord
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  • J. Van Os
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  • R. Van Winkel
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  • J. Veldink
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  • D. Walsh
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  • A.G. Wang
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  • D. Wiersma
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  • D.B. Wildenauer
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  • H.J. Williams
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  • Nigel M.A. Williams, School of Medicine, Cardiff University, United Kingdom
  • B. Wormley
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  • S. Zammit
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  • Patrick F. Sullivan, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States, United States
  • M.C. O'Donovan
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  • Mark J. Daly, Massachusetts General Hospital, Center for Computational and Integrative Biology, Boston, United States, United States
  • P.V. Gejman
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 = 0.055, p = 2.1 × 10 ) and with IQ in the entire sample (R = 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.
Original languageEnglish
JournalPsychological Medicine
Volume43
Issue12
Pages (from-to)2563-2570
Number of pages8
ISSN0033-2917
DOIs
Publication statusPublished - 2013

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