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 (R2=0.055, p=2.1×10−7) and with IQ in the entire sample (R2=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.

Integrating Genetics and Social Science: Genetic Risk Scores

“…To our knowledge such studies have not yet been conducted. But proof of concept can be seen in two recent studies showing that genetic risks discovered in GWAS of schizophrenia are related to cognitive ability and cognitive decline (McIntosh et al 2013; Lencz et al 2014), although this finding remains contentious (van Scheltinga et al 2013). …”

Polygenic risk scores in imaging genetics: Usefulness and applications

“…It has also been used to differentiate genetically, for example, schizophrenia and autism (Vorstman et al, 2013) or schizophrenia and intelligence (van Scheltinga et al, 2013). The schizophrenia PRS has been correlated with quantitative measures of psychosis in terms of symptoms scales (Derks et al, 2012) and neuroimaging measures (Walton et al, 2013).…”

Copy number deletion burden is associated with cognitive, structural, and resting-state network differences in patients with schizophrenia

“…A further study by the same group [6] found no link between total deletion burden and intelligence as measured by the Wechsler Adult Intelligence Scale (WAIS). However, this may be due to the inclusion of all deletions regardless of Page 4 of 38 A c c e p t e d M a n u s c r i p t 4 frequency and could explain the discrepancy between their findings and the findings of Yeo et al [4].…”