title: Polygenic risk for schizophrenia is associated with cognitive change between childhood and old age.
abstract: 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.
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. andrew.mcintosh@ed.ac.uk
authors: Andrew M
authors: AM
authors: McIntosh
authors: Alan
authors: A
authors: Gow
authors: Michelle
authors: M
authors: Luciano
authors: Gail
authors: G
authors: Davies
authors: David C
authors: DC
authors: Liewald
authors: Sarah E
authors: SE
authors: Harris
authors: Janie
authors: J
authors: Corley
authors: Jeremy
authors: J
authors: Hall
authors: John M
authors: JM
authors: Starr
authors: David J
authors: DJ
authors: Porteous
authors: Albert
authors: A
authors: Tenesa
authors: Peter M
authors: PM
authors: Visscher
authors: Ian J
authors: IJ
authors: Deary
mesh_terms: D000368:Aged; D000375:Aging; D002648:Child; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D007360:Intelligence; D008297:Male; D009483:Neuropsychological Tests; D012111:Residence Characteristics; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D012565:Schizophrenic Psychology