title: Genetic Variation in Schizophrenia Liability is Shared With Intellectual Ability and Brain Structure.
abstract: Alterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying these genetic markers using a multivariate twin modeling approach can provide novel leads for (genetic) pathways of schizophrenia development.
  
  
  
  In a sample of 70 twins discordant for schizophrenia and 130 healthy control twins, structural equation modeling was applied to quantify unique contributions of genetic and environmental factors on human brain structure (cortical thickness, cortical surface and global white matter fractional anisotropy [FA]), intellectual ability and schizophrenia liability.
  
  
  
  In total, up to 28.1% of the genetic variance (22.8% of total variance) in schizophrenia liability was shared with intelligence quotient (IQ), global-FA, cortical thickness, and cortical surface. The strongest contributor was IQ, sharing on average 16.4% of the genetic variance in schizophrenia liability, followed by cortical thickness (6.3%), global-FA (4.7%) and cortical surface (0.5%). Furthermore, we found that up to 57.4% of the variation due to environmental factors (4.6% of total variance) in schizophrenia was shared with IQ (34.2%) and cortical surface (13.4%).
  
  
  
  Intellectual ability, FA and cortical thickness show significant and independent shared genetic variance with schizophrenia liability. This suggests that measuring brain-imaging phenotypes helps explain genetic variance in schizophrenia liability that is not captured by variation in IQ.
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands m.bohlken@umcutrecht.nl.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Bohlken
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Brouwer
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: René C W
authors.initials: RC
authors.lastname: Mandl
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hilleke E
authors.initials: HE
authors.lastname: Hulshoff Pol
mesh_terms: D000328:Adult; D001076:Aptitude; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000235:genetics*; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: IQ; MRI; cortex; heritability; schizophrenia; white matter