Schizophrenia Genetic Variants are not Associated with Intelligence


Autoria(s): 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.; Scolnick, E.; Cichon, S.; St Clair, D.; Corvin, A.; Gurling, H.; Werge, T.; Rujescu, D.; Blackwood, D. H. R.; Pato, C. N.; Malhotra, A. K.; Purcell, S.; Dudbridge, F.; Neale, B. 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.; 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.; Bass, N.; Bergen, S. E.; Black, D. W.; Børglum, A. D.; Brown, M. A.; Bruggeman, R.; Buccola, N. G.; Byerley, W. F.; Cahn, W.; Cantor, R. M.; Carr, V. J.; Catts, S. V.; Choudhury, K.; Cloninger, C. R.; Cormican, P.; Craddock, N.; Danoy, P. A.; Datta, S.; De Haan, L.; Demontis, D.; Dikeos, D.; Djurovic, S.; Donnelly, P.; Donohoe, G.; Duong, L.; Dwyer, S.; Fink-Jensen, A.; Freedman, R.; Freimer, N. B.; Friedl, M.; Georgieva, L.; Giegling, I.; Gill, M.; Glenthøj, B.; Godard, S.; Hamshere, M.; Hansen, M.; Hansen, T.; Hartmann, A. M.; Henskens, F. A.; Hougaard, D. M.; Hultman, C. M.; Ingason, A.; Jablensky, A. V.; Jakobsen, K. D.; Jay, M.; Jürgens, G.; Kahn, R. S.; Keller, M. C.; Kenis, G.; Kenny, E.; Kim, Y.; Kirov, G. K.; Konnerth, H.; Konte, B.; Krabbendam, L.; Krasucki, R.; Lasseter, V. K.; Laurent, C.; Lawrence, J.; Lencz, T.; Lerer, F. B.; Liang, K. Y.; Lichtenstein, P.; Lieberman, J. A.; Linszen, D. H.; Lönnqvist, J.; Loughland, C. M.; Maclean, A. W.; Maher, B. S.; Maier, W.; Mallet, J.; Malloy, P.; Mattheisen, M.; Mattingsdal, M.; McGhee, K. A.; McGrath, J. J.; McIntosh, A.; McLean, D. E.; McQuillin, A.; Melle, I.; Michie, P. T.; Milanova, V.; Morris, D. W.; Mors, O.; Mortensen, P. B.; Moskvina, V.; Muglia, P.; Myin-Germeys, I.; Nertney, D. A.; Nestadt, G.; Nielsen, J.; 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.; Pantelis, C.; Papadimitriou, G.; Pato, M. T.; Peltonen, L.; Petursson, H.; Pickard, B.; Pimm, J.; Pulver, A. E.; Puri, V.; Quested, D.; 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.; Scott, R. J.; Shi, J.; Sigurdsson, E.; Silverman, J. M.; Spencer, C. C. A.; Stefansson, K.; Strange, A.; Strengman, E.; Stroup, T. S.; Suvisaari, J.; 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.; 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.; Gejman, P. V.
Data(s)

2013

Resumo

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. © Cambridge University Press 2013.

Identificador

http://eprints.qut.edu.au/89274/

Publicador

Cambridge University Press

Relação

DOI:10.1017/S0033291713000196

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., Scolnick, E., Cichon, S., St Clair, D., Corvin, A., Gurling, H., Werge, T., Rujescu, D., Blackwood, D. H. R., Pato, C. N., Malhotra, A. K., Purcell, S., Dudbridge, F., Neale, B. 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., 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., Bass, N., Bergen, S. E., Black, D. W., Børglum, A. D., Brown, M. A., Bruggeman, R., Buccola, N. G., Byerley, W. F., Cahn, W., Cantor, R. M., Carr, V. J., Catts, S. V., Choudhury, K., Cloninger, C. R., Cormican, P., Craddock, N., Danoy, P. A., Datta, S., De Haan, L., Demontis, D., Dikeos, D., Djurovic, S., Donnelly, P., Donohoe, G., Duong, L., Dwyer, S., Fink-Jensen, A., Freedman, R., Freimer, N. B., Friedl, M., Georgieva, L., Giegling, I., Gill, M., Glenthøj, B., Godard, S., Hamshere, M., Hansen, M., Hansen, T., Hartmann, A. M., Henskens, F. A., Hougaard, D. M., Hultman, C. M., Ingason, A., Jablensky, A. V., Jakobsen, K. D., Jay, M., Jürgens, G., Kahn, R. S., Keller, M. C., Kenis, G., Kenny, E., Kim, Y., Kirov, G. K., Konnerth, H., Konte, B., Krabbendam, L., Krasucki, R., Lasseter, V. K., Laurent, C., Lawrence, J., Lencz, T., Lerer, F. B., Liang, K. Y., Lichtenstein, P., Lieberman, J. A., Linszen, D. H., Lönnqvist, J., Loughland, C. M., Maclean, A. W., Maher, B. S., Maier, W., Mallet, J., Malloy, P., Mattheisen, M., Mattingsdal, M., McGhee, K. A., McGrath, J. J., McIntosh, A., McLean, D. E., McQuillin, A., Melle, I., Michie, P. T., Milanova, V., Morris, D. W., Mors, O., Mortensen, P. B., Moskvina, V., Muglia, P., Myin-Germeys, I., Nertney, D. A., Nestadt, G., Nielsen, J., 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., Pantelis, C., Papadimitriou, G., Pato, M. T., Peltonen, L., Petursson, H., Pickard, B., Pimm, J., Pulver, A. E., Puri, V., Quested, D., 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., Scott, R. J., Shi, J., Sigurdsson, E., Silverman, J. M., Spencer, C. C. A., Stefansson, K., Strange, A., Strengman, E., Stroup, T. S., Suvisaari, J., 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., 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., & Gejman, P. V. (2013) Schizophrenia Genetic Variants are not Associated with Intelligence. Psychological Medicine, 43(12), pp. 2563-2570.

Direitos

Copyright Cambridge University Press 2013

Fonte

Faculty of Health; Institute of Health and Biomedical Innovation

Palavras-Chave #Cognition #deletion #duplication #endophenotype #IQ #polygenic #SNP #adult #article #copy number variation #female #genetic association #genetic predisposition #genetics #human #intelligence #male #multifactorial inheritance #schizophrenia #single nucleotide polymorphism #Wechsler Intelligence Scale #DNA Copy Number Variations #Endophenotypes #Genetic Predisposition to Disease #Genome-Wide Association Study #Humans #Polymorphism #Single Nucleotide #Wechsler Scales
Tipo

Journal Article