TY - JOUR
T1 - Schizophrenia genetic variants are not associated with intelligence
AU - Scheltinga, A. F. Terwisscha van
AU - Bakker, S. C.
AU - Haren, N. E. M. van
AU - Derks, E. M.
AU - Buizer-Voskamp, J. E.
AU - Cahn, W.
AU - Ripke, S.
AU - Ophoff, R. A.
AU - Kahn, R. S.
AU - Craddock, Nicholas John
AU - Escott-Price, Valentina
AU - Georgieva, Lyudmila
AU - Hamshere, Marian Lindsay
AU - Holmans, Peter Alan
AU - Kirov, George
AU - O'Donovan, Michael Conlon
AU - Owen, Michael John
AU - Ruderfer, Doug
AU - Williams, Hywel
AU - Williams, Nigel Melville
AU - Zammit, Stanley
PY - 2013/12/1
Y1 - 2013/12/1
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.
U2 - 10.1017/S0033291713000196
DO - 10.1017/S0033291713000196
M3 - Article (Academic Journal)
C2 - 23410598
SN - 0033-2917
VL - 43
SP - 2563
EP - 2570
JO - Psychological Medicine
JF - Psychological Medicine
IS - 12
ER -