Schizophrenia genetic variants are not associated with intelligence

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, R. S. Kahn, S. Ripke, A. R. Sanders, K. S. Kendler, D. F. Levinson, P. Sklar, P. A. Holmans, D. Y. Lin, J. Duan, R. A. Ophoff, O. A. Andreassen, E. ScolnickS. Cichon, D. St Clair, A. Corvin, H. Gurling, T. Werge, D. Rujescu, D. H.R. Blackwood, C. N. Pato, A. K. Malhotra, S. Purcell, F. Dudbridge, B. M. Neale, L. Rossin, P. M. Visscher, D. Posthuma, D. M. Ruderfer, A. Fanous, H. Stefansson, S. Steinberg, B. J. Mowry, V. Golimbet, M. De Hert, E. G. Jönsson, I. Bitter, O. P.H. Pietiläinen, D. A. Collier, S. Tosato, I. Agartz, M. Albus, M. Alexander, R. L. Amdur, F. Amin, N. Bass, S. E. Bergen, D. W. Black, A. D. Børglum, M. A. Brown, R. Bruggeman, N. G. Buccola, W. F. Byerley, W. Cahn, R. M. Cantor, V. J. Carr, S. V. Catts, K. Choudhury, C. R. Cloninger, P. Cormican, N. Craddock, P. A. Danoy, S. Datta, L. De Haan, D. Demontis, D. Dikeos, S. Djurovic, P. Donnelly, G. Donohoe, L. Duong, S. Dwyer, A. Fink-Jensen, R. Freedman, N. B. Freimer, M. Friedl, L. Georgieva, I. Giegling, M. Gill, B. Glenthøj, S. Godard, M. Hamshere, M. Hansen, T. Hansen, A. M. Hartmann, F. A. Henskens, D. M. Hougaard, C. M. Hultman, A. Ingason, A. V. Jablensky, K. D. Jakobsen, M. Jay, G. Jürgens, R. S. Kahn, M. C. Keller, G. Kenis, E. Kenny, Y. Kim, G. K. Kirov, H. Konnerth, B. Konte, L. Krabbendam, R. Krasucki, V. K. Lasseter, C. Laurent, J. Lawrence, T. Lencz, F. B. Lerer, K. Y. Liang, P. Lichtenstein, J. A. Lieberman, D. H. Linszen, J. Lönnqvist, C. M. Loughland, A. W. Maclean, B. S. Maher, W. Maier, J. Mallet, P. Malloy, M. Mattheisen, M. Mattingsdal, K. A. McGhee, J. J. McGrath, A. McIntosh, D. E. McLean, A. McQuillin, I. Melle, P. T. Michie, V. Milanova, D. W. Morris, O. Mors, P. B. Mortensen, V. Moskvina, P. Muglia, I. Myin-Germeys, D. A. Nertney, G. Nestadt, J. Nielsen, I. Nikolov, M. Nordentoft, Nadine Norton, M. M. Nöthen, C. T. O'Dushlaine, A. Olincy, L. Olsen, F. A. O'Neill, T. F. Ørntoft, M. J. Owen, C. Pantelis, G. Papadimitriou, M. T. Pato, L. Peltonen, H. Petursson, B. Pickard, J. Pimm, A. E. Pulver, V. Puri, D. Quested, E. M. Quinn, H. B. Rasmussen, J. M. Réthelyi, R. Ribble, M. Rietschel, B. P. Riley, M. Ruggeri, U. Schall, T. G. Schulze, S. G. Schwab, R. J. Scott, J. Shi, E. Sigurdsson, J. M. Silverman, C. C.A. Spencer, K. Stefansson, A. Strange, E. Strengman, T. S. Stroup, J. Suvisaari, L. Terenius, S. Thirumalai, J. H. Thygesen, S. Timm, D. Toncheva, E. Van Den Oord, J. Van Os, R. Van Winkel, J. Veldink, D. Walsh, A. G. Wang, D. Wiersma, D. B. Wildenauer, H. J. Williams, N. M. Williams, B. Wormley, S. Zammit, P. F. Sullivan, M. C. O'Donovan, M. J. Daly, P. V. Gejman

Research output: Contribution to journalArticle

28 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)2563-2570
Number of pages8
JournalPsychological Medicine
Volume43
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

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

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health

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  • Cite this

    Van Scheltinga, A. F. T., Bakker, S. C., Van Haren, N. E. M., Derks, E. M., Buizer-Voskamp, J. E., Cahn, W., Ripke, S., Ophoff, R. A., Kahn, R. S., Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., Lin, D. Y., Duan, J., Ophoff, R. A., Andreassen, O. A., ... Gejman, P. V. (2013). Schizophrenia genetic variants are not associated with intelligence. Psychological Medicine, 43(12), 2563-2570. https://doi.org/10.1017/S0033291713000196