Schizotypy, cognitive performance, and genetic risk for schizophrenia in a non-clinical population

• Schizophrenia risk alleles do not reliably predict measures of schizotypy.
• Higher summed genetic risk is correlated with lower mental rotation skill in males.
• Lack of linear, genetic continuity between clinical and healthy populations.

Schizophrenia risk alleles are expected to mediate effects on cognitive task performance, and aspects of personality including schizotypy, in nonclinical populations. We investigated how 32 of the best-validated schizophrenia risk alleles, singly and as summed genetic risk, were related to measures of schizotypal personality and measures of two aspects of cognitive performance, verbal skills (vocabulary) and visual-spatial skills (mental rotation), in healthy individuals. Summed genetic risk score was not associated with levels of total schizotypy or its three main subscales. Similarly, genotypic variation at none of the individual risk loci was related to cognitive performance measures, after correction for multiple tests. Higher overall genetic risk score was, however, associated with lower performance on the mental rotation test in males, with a broad set of loci contributing to this effect. These results imply that there is a lack of linear, genetically-based continuity connecting schizotypal cognition with the expression of schizophrenia itself, and indicate that, for males, higher genetic risk of schizophrenia exerts negative effects on visual-spatial skills, as measured by mental rotation.