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.
Key Words
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Article info
Publication history
Published online: February 18, 2013
Accepted:
January 9,
2013
Received in revised form:
December 17,
2012
Received:
October 11,
2012
Identification
Copyright
© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
