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. Scolnick; S. 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; Kung-Yee 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; N. 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; Ann 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

doi:10.1017/S0033291713000196

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, Kung-Yee 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, N. 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, Ann 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 journal › Article › peer-review

29 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 language	English (US)
Pages (from-to)	2563-2570
Number of pages	8
Journal	Psychological medicine
Volume	43
Issue number	12
DOIs	https://doi.org/10.1017/S0033291713000196
State	Published - Dec 2013

Keywords

Cognition
IQ
SNP
deletion
duplication
endophenotype
polygenic

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

Access to Document

10.1017/S0033291713000196

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

Van Scheltinga, AFT, Bakker, SC, Van Haren, NEM, Derks, EM, Buizer-Voskamp, JE, Cahn, W, Ripke, S, Ophoff, RA, Kahn, RS, Ripke, S, Sanders, AR, Kendler, KS, Levinson, DF, Sklar, P, Holmans, PA, Lin, DY, Duan, J, Ophoff, RA, Andreassen, OA, Scolnick, E, Cichon, S, St Clair, D, Corvin, A, Gurling, H, Werge, T, Rujescu, D, Blackwood, DHR, Pato, CN, Malhotra, AK, Purcell, S, Dudbridge, F, Neale, BM, Rossin, L, Visscher, PM, Posthuma, D, Ruderfer, DM, Fanous, A, Stefansson, H, Steinberg, S, Mowry, BJ, Golimbet, V, De Hert, M, Jönsson, EG, Bitter, I, Pietiläinen, OPH, Collier, DA, Tosato, S, Agartz, I, Albus, M, Alexander, M, Amdur, RL, Amin, F, Bass, N, Bergen, SE, Black, DW, Børglum, AD, Brown, MA, Bruggeman, R, Buccola, NG, Byerley, WF, Cahn, W, Cantor, RM, Carr, VJ, Catts, SV, Choudhury, K, Cloninger, CR, Cormican, P, Craddock, N, Danoy, PA, 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, NB, Friedl, M, Georgieva, L, Giegling, I, Gill, M, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, AM, Henskens, FA, Hougaard, DM, Hultman, CM, Ingason, A, Jablensky, AV, Jakobsen, KD, Jay, M, Jürgens, G, Kahn, RS, Keller, MC, Kenis, G, Kenny, E, Kim, Y, Kirov, GK, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, VK, Laurent, C, Lawrence, J, Lencz, T, Lerer, FB, Liang, K-Y, Lichtenstein, P, Lieberman, JA, Linszen, DH, Lönnqvist, J, Loughland, CM, Maclean, AW, Maher, BS, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, McGhee, KA, McGrath, JJ, McIntosh, A, McLean, DE, McQuillin, A, Melle, I, Michie, PT, Milanova, V, Morris, DW, Mors, O, Mortensen, PB, Moskvina, V, Muglia, P, Myin-Germeys, I, Nertney, DA, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, MM, O'Dushlaine, CT, Olincy, A, Olsen, L, O'Neill, FA, Ørntoft, TF, Owen, MJ, Pantelis, C, Papadimitriou, G, Pato, MT, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, AE, Puri, V, Quested, D, Quinn, EM, Rasmussen, HB, Réthelyi, JM, Ribble, R, Rietschel, M, Riley, BP, Ruggeri, M, Schall, U, Schulze, TG, Schwab, SG, Scott, RJ, Shi, J, Sigurdsson, E, Silverman, JM, Spencer, CCA, Stefansson, K, Strange, A, Strengman, E, Stroup, TS, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, JH, Timm, S, Toncheva, D, Van Den Oord, E, Van Os, J, Van Winkel, R, Veldink, J, Walsh, D, Wang, AG, Wiersma, D, Wildenauer, DB, Williams, HJ, Williams, NM, Wormley, B, Zammit, S, Sullivan, PF, O'Donovan, MC, Daly, MJ & Gejman, PV 2013, 'Schizophrenia genetic variants are not associated with intelligence', Psychological medicine, vol. 43, no. 12, pp. 2563-2570. https://doi.org/10.1017/S0033291713000196

@article{b199ee5e46b44b2ba0879430b0d2c266,

title = "Schizophrenia genetic variants are not associated with intelligence",

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.",

keywords = "Cognition, IQ, SNP, deletion, duplication, endophenotype, polygenic",

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

year = "2013",

month = dec,

doi = "10.1017/S0033291713000196",

language = "English (US)",

volume = "43",

pages = "2563--2570",

journal = "Psychological medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "12",

}

TY - JOUR

T1 - Schizophrenia genetic variants are not associated with intelligence

AU - Van Scheltinga, A. F.Terwisscha

AU - Bakker, S. C.

AU - Van Haren, N. E.M.

AU - Derks, E. M.

AU - Buizer-Voskamp, J. E.

AU - Cahn, W.

AU - Ripke, S.

AU - Ophoff, R. A.

AU - Kahn, R. S.

AU - Ripke, S.

AU - Sanders, A. R.

AU - Kendler, K. S.

AU - Levinson, D. F.

AU - Sklar, P.

AU - Holmans, P. A.

AU - Lin, D. Y.

AU - Duan, J.

AU - Ophoff, R. A.

AU - Andreassen, O. A.

AU - Scolnick, E.

AU - Cichon, S.

AU - St Clair, D.

AU - Corvin, A.

AU - Gurling, H.

AU - Werge, T.

AU - Rujescu, D.

AU - Blackwood, D. H.R.

AU - Pato, C. N.

AU - Malhotra, A. K.

AU - Purcell, S.

AU - Dudbridge, F.

AU - Neale, B. M.

AU - Rossin, L.

AU - Visscher, P. M.

AU - Posthuma, D.

AU - Ruderfer, D. M.

AU - Fanous, A.

AU - Stefansson, H.

AU - Steinberg, S.

AU - Mowry, B. J.

AU - Golimbet, V.

AU - De Hert, M.

AU - Jönsson, E. G.

AU - Bitter, I.

AU - Pietiläinen, O. P.H.

AU - Collier, D. A.

AU - Tosato, S.

AU - Agartz, I.

AU - Albus, M.

AU - Alexander, M.

AU - Amdur, R. L.

AU - Amin, F.

AU - Bass, N.

AU - Bergen, S. E.

AU - Black, D. W.

AU - Børglum, A. D.

AU - Brown, M. A.

AU - Bruggeman, R.

AU - Buccola, N. G.

AU - Byerley, W. F.

AU - Cahn, W.

AU - Cantor, R. M.

AU - Carr, V. J.

AU - Catts, S. V.

AU - Choudhury, K.

AU - Cloninger, C. R.

AU - Cormican, P.

AU - Craddock, N.

AU - Danoy, P. A.

AU - Datta, S.

AU - De Haan, L.

AU - Demontis, D.

AU - Dikeos, D.

AU - Djurovic, S.

AU - Donnelly, P.

AU - Donohoe, G.

AU - Duong, L.

AU - Dwyer, S.

AU - Fink-Jensen, A.

AU - Freedman, R.

AU - Freimer, N. B.

AU - Friedl, M.

AU - Georgieva, L.

AU - Giegling, I.

AU - Gill, M.

AU - Glenthøj, B.

AU - Godard, S.

AU - Hamshere, M.

AU - Hansen, M.

AU - Hansen, T.

AU - Hartmann, A. M.

AU - Henskens, F. A.

AU - Hougaard, D. M.

AU - Hultman, C. M.

AU - Ingason, A.

AU - Jablensky, A. V.

AU - Jakobsen, K. D.

AU - Jay, M.

AU - Jürgens, G.

AU - Kahn, R. S.

AU - Keller, M. C.

AU - Kenis, G.

AU - Kenny, E.

AU - Kim, Y.

AU - Kirov, G. K.

AU - Konnerth, H.

AU - Konte, B.

AU - Krabbendam, L.

AU - Krasucki, R.

AU - Lasseter, V. K.

AU - Laurent, C.

AU - Lawrence, J.

AU - Lencz, T.

AU - Lerer, F. B.

AU - Liang, Kung-Yee

AU - Lichtenstein, P.

AU - Lieberman, J. A.

AU - Linszen, D. H.

AU - Lönnqvist, J.

AU - Loughland, C. M.

AU - Maclean, A. W.

AU - Maher, B. S.

AU - Maier, W.

AU - Mallet, J.

AU - Malloy, P.

AU - Mattheisen, M.

AU - Mattingsdal, M.

AU - McGhee, K. A.

AU - McGrath, J. J.

AU - McIntosh, A.

AU - McLean, D. E.

AU - McQuillin, A.

AU - Melle, I.

AU - Michie, P. T.

AU - Milanova, V.

AU - Morris, D. W.

AU - Mors, O.

AU - Mortensen, P. B.

AU - Moskvina, V.

AU - Muglia, P.

AU - Myin-Germeys, I.

AU - Nertney, D. A.

AU - Nestadt, G.

AU - Nielsen, J.

AU - Nikolov, I.

AU - Nordentoft, M.

AU - Norton, N.

AU - Nöthen, M. M.

AU - O'Dushlaine, C. T.

AU - Olincy, A.

AU - Olsen, L.

AU - O'Neill, F. A.

AU - Ørntoft, T. F.

AU - Owen, M. J.

AU - Pantelis, C.

AU - Papadimitriou, G.

AU - Pato, M. T.

AU - Peltonen, L.

AU - Petursson, H.

AU - Pickard, B.

AU - Pimm, J.

AU - Pulver, Ann E

AU - Puri, V.

AU - Quested, D.

AU - Quinn, E. M.

AU - Rasmussen, H. B.

AU - Réthelyi, J. M.

AU - Ribble, R.

AU - Rietschel, M.

AU - Riley, B. P.

AU - Ruggeri, M.

AU - Schall, U.

AU - Schulze, T. G.

AU - Schwab, S. G.

AU - Scott, R. J.

AU - Shi, J.

AU - Sigurdsson, E.

AU - Silverman, J. M.

AU - Spencer, C. C.A.

AU - Stefansson, K.

AU - Strange, A.

AU - Strengman, E.

AU - Stroup, T. S.

AU - Suvisaari, J.

AU - Terenius, L.

AU - Thirumalai, S.

AU - Thygesen, J. H.

AU - Timm, S.

AU - Toncheva, D.

AU - Van Den Oord, E.

AU - Van Os, J.

AU - Van Winkel, R.

AU - Veldink, J.

AU - Walsh, D.

AU - Wang, A. G.

AU - Wiersma, D.

AU - Wildenauer, D. B.

AU - Williams, H. J.

AU - Williams, N. M.

AU - Wormley, B.

AU - Zammit, S.

AU - Sullivan, P. F.

AU - O'Donovan, M. C.

AU - Daly, M. J.

AU - Gejman, P. V.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - Cognition

KW - IQ

KW - SNP

KW - deletion

KW - duplication

KW - endophenotype

KW - polygenic

UR - http://www.scopus.com/inward/record.url?scp=84887494584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887494584&partnerID=8YFLogxK

U2 - 10.1017/S0033291713000196

DO - 10.1017/S0033291713000196

M3 - Article

C2 - 23410598

AN - SCOPUS:84887494584

SN - 0033-2917

VL - 43

SP - 2563

EP - 2570

JO - Psychological medicine

JF - Psychological medicine

IS - 12

ER -

Schizophrenia genetic variants are not associated with intelligence

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this