Polygenic Risk for Schizophrenia is Associated with Cognitive Change Between Childhood and Old Age

Background: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS.

Methods: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS.

Results: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis.

Conclusions: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.