title: Principal components of heritability from neurocognitive domains differ between families with schizophrenia and control subjects.
abstract: OBJECTIVE
  Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls.
  
  
  METHODS
  African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three PCH, PCH1-PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample.
  
  
  RESULTS
  PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1-PCH3 or individual neurocognitive measures was discovered.
  
  
  CONCLUSIONS
  PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members.
authors.affiliation: Department of Epidemiology and International Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Wiener
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.forename: Monica
authors.initials: M
authors.lastname: Calkins
authors.forename: Joel
authors.initials: J
authors.lastname: Wood
authors.forename: Vishwajit
authors.initials: V
authors.lastname: Nimgaonkar
authors.forename: Ruben
authors.initials: R
authors.lastname: Gur
authors.forename: L DiAnne
authors.initials: LD
authors.lastname: Bradford
authors.forename: Jan
authors.initials: J
authors.lastname: Richard
authors.forename: Neil
authors.initials: N
authors.lastname: Edwards
authors.forename: Robert
authors.initials: R
authors.lastname: Savage
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwentus
authors.forename: Trina
authors.initials: T
authors.lastname: Allen
authors.forename: Joseph
authors.initials: J
authors.lastname: McEvoy
authors.forename: Alberto
authors.initials: A
authors.lastname: Santos
authors.forename: Raquel
authors.initials: R
authors.lastname: Gur
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Rodney
authors.initials: R
authors.lastname: Go
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000523:psychology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000208:ethnology / Q000235:genetics* / Q000523:psychology; D005190:Family / Q000523:psychology*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000235:genetics* / Q000523:psychology; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D012565:Schizophrenic Psychology