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.
  
  
  METHODS
  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.
authors: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
authors: A F Terwisscha
authors: AF
authors: van Scheltinga
authors: S C
authors: SC
authors: Bakker
authors: N E M
authors: NE
authors: van Haren
authors: E M
authors: EM
authors: Derks
authors: J E
authors: JE
authors: Buizer-Voskamp
authors: W
authors: W
authors: Cahn
authors: S
authors: S
authors: Ripke
authors: R A
authors: RA
authors: Ophoff
authors: R S
authors: RS
authors: Kahn
mesh_terms: D000328:Adult; D056915:DNA Copy Number Variations / Q000235:genetics; D058068:Endophenotypes; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D014888:Wechsler Scales