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Higher genetic risk of schizophrenia is associated with lower cognitive performance in healthy individuals

By Rebecca Shafee, Pranav Nanda, Jaya L Padmanabhan, Neeraj Tandon, Ney Alliey-Rodriguez, Richard S.E. Keefe, Scot K Hill, Jeffrey R Bishop, Brett A Clementz, Carol A Tamminga, Elliot S Gershon, Godfrey D Pearlson, Matcheri S Keshavan, John A Sweeney, Elise B Robinson, Steven A McCarroll

Posted 27 Jan 2017
bioRxiv DOI: 10.1101/103622

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of the genetic risk of schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychosis patients; a measure of premorbid intelligence that is minimally affected by psychosis (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide SNP data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was associated with lower BACS scores (r = -0.19, p = 1 × 10-4 at PT = 1 × 10-4) but did not associate with WRAT or EY, suggesting that these areas of cognition vary in their etiologic relationships with schizophrenia. Among individuals with psychosis, PRSSCZ did not associate with variation in cognitive performance. These findings suggest that the same cognitive abilities that are disrupted in psychotic disorders are also associated with schizophrenia genetic risk in the general population. Specific cognitive phenotypes, independent of education or general intelligence, could be more deeply studied for insight into the specific processes affected by the genetic influences on psychosis.

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