title: Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders.
abstract: General cognitive function predicts psychiatric illness across the life course. This study examines the role of pleiotropy in explaining the link between cognitive function and psychiatric disorder.
  
  
  
  We used two large genome-wide association study data sets on cognitive function-one from older age, n = 53,949, and one from childhood, n = 12,441. We also used genome-wide association study data on educational attainment, n = 95,427, to examine the validity of its use as a proxy phenotype for cognitive function. Using a new method, linkage disequilibrium regression, we derived genetic correlations, free from the confounding of clinical state between psychiatric illness and cognitive function.
  
  
  
  We found a genetic correlation of .711 (p = 2.26e-12) across the life course for general cognitive function. We also showed a positive genetic correlation between autism spectrum disorder and cognitive function in childhood (rg = .360, p = .0009) and for educational attainment (rg = .322, p = 1.37e-5) but not in older age. In schizophrenia, we found a negative genetic correlation between older age cognitive function (rg = -.231, p = 3.81e-12) but not in childhood or for educational attainment. For Alzheimer's disease, we found negative genetic correlations with childhood cognitive function (rg = -.341, p = .001), educational attainment (rg = -.324, p = 1.15e-5), and with older age cognitive function (rg = -.324, p = 1.78e-5).
  
  
  
  The pleiotropy exhibited between cognitive function and psychiatric disorders changed across the life course. These age-dependent associations might explain why negative selection has not removed variants causally associated with autism spectrum disorder or schizophrenia.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Departments of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: W David
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Departments of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Departments of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Departments of Psychology, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: ian.deary@ed.ac.uk.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000375:Aging / Q000235:genetics*; D003072:Cognition Disorders / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology* / Q000235:genetics*; D015201:Meta-Analysis as Topic
keywords: Aging; Autism; Cognitive function; Genetics; Pleiotropy; Schizophrenia