Schizophrenia genetic variants are not associated with intelligence

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

Schizophrenia genetic variants are not associated with intelligence

journal contribution

posted on 2025-05-08, 15:04 authored by A. F. Terwisscha van Scheltinga, S. C. Bakker, K. S. Kendler, G. K. Kirov, H. Konnerth, B. Konte, L. Krabbendam, R. Krasucki, V. K. Lasseter, C. Laurent, J. Lawrence, T. Lencz, F. B. Lerer, D. F. Levinson, K.-Y. Liang, P. Lichtenstein, J. A. Lieberman, D. H. Linszen, J. Lönnqvist, Carmel LoughlandCarmel Loughland, A. W. Maclean, B. S. Maher, W. Maier, J. Mallet, P. Sklar, P. Malloy, M. Mattheisen, M. Mattingsdal, K. A. McGhee, J. J. McGrath, A. McIntosh, D. E. McLean, A. McQuillin, I. Melle, Patricia MichiePatricia Michie, P. A. Holmans, V. Milanova, D. W. Morris, O. Mors, P. B. Mortensen, V. Moskvina, P. Muglia, I. Myin-Germeys, D. A. Nertney, G. Nestadt, J. Nielsen, D.-Y. Lin, I. Nikolov, M. Nordentoft, N. Norton, M. M. Nöthen, C. T. O'Dushlaine, A. Olincy, L. Olsen, F. A. O'Neill, T. F. Ørntoft, M. J. Owen, J. Duan, C. Pantelis, G. Papadimitriou, M. T. Pato, L. Peltonen, H. Petursson, B. Pickard, J. Pimm, A. E. Pulver, V. Puri, D. Quested, O. A. Andreassen, 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, E. Scolnick, Rodney ScottRodney Scott, J. Shi, E. Sigurdsson, J. M. Silverman, C. C. A. Spencer, K. Stefansson, A. Strange, E. Strengman, T. S. Stroup, J. Suvisaari, S. Cichon, 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, D. St Clair, 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, N. E. M. van Haren, A. Corvin, P. V. Gejman, H. Gurling, T. Werge, D. Rujescu, D. H. R. Blackwood, C. N. Pato, A. K. Malhotra, S. Purcell, F. Dudbridge, B. M. Neale, E. M. Derks, L. Rossin, P. M. Visscher, D. Posthuma, D. M. Ruderfer, A. Fanous, H. Stefansson, S. Steinberg, B. J. Mowry, V. Golimbet, M. De Hert, J. E. Buizer-Voskamp, 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, W. Cahn, N. Bass, S. E. Bergen, D. W. Black, A. D. Børglum, M. A. Brown, R. Bruggeman, N. G. Buccola, W. F. Byerley, R. M. Cantor, V. J. Carr, S. Ripke, S. V. Catts, K. Choudhury, C. R. Cloninger, P. Cormican, N. Craddock, P. A. Danoy, S. Datta, L. De Haan, D. Demontis, D. Dikeos, R. A. Ophoff, S. Djurovic, P. Donnelly, G. Donohoe, L. Duong, S. Dwyer, A. Fink-Jensen, R. Freedman, N. B. Freimer, M. Friedl, L. Georgieva, R. S. Kahn, I. Giegling, M. Gill, B. Glenthøj, S. Godard, M Hamshere, M. Hansen, T. Hansen, A. M. Hartmann, Frans HenskensFrans Henskens, D. M. Hougaard, A. R. Sanders, C. M. Hultman, A. Ingason, A. V. Jablensky, K. D. Jakobsen, M. Jay, G. Jürgens, M. C. Keller, G. Kenis, E. Kenny, Y. Kim

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.

History

Journal title

Psychological Medicine

Volume

43

Issue

12

Pagination

2563-2570

Publisher

Cambridge University Press

Language

en, English

College/Research Centre

Faculty of Engineering and Built Environment

School

School of Electrical Engineering and Computer Science

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Keywords

cognition deletion duplication endophenotype IQ polygenic SNP

Schizophrenia genetic variants are not associated with intelligence

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