title: Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees.
abstract: BACKGROUND
  We report on copy number variants (CNVs) found in Palauan subjects ascertained for schizophrenia and related psychotic disorders in extended pedigrees in Palau. We compare CNVs found in this Oceanic population with those seen in other samples, typically of European ancestry. Assessing CNVs in Palauan extended pedigrees yields insight into the evolution of risk CNVs, such as how they arise, are transmitted, and are lost from populations by stochastic or selective processes, none of which are easily measured from case-control samples.
  
  
  METHODS
  DNA samples from 197 subjects affected with schizophrenia and related psychotic disorders, 185 of their relatives, and 159 control subjects were successfully characterized for CNVs using Affymetrix Genomewide Human SNP Array 5.0.
  
  
  RESULTS
  Copy number variants thought to be associated with risk for schizophrenia and related disorders also occur in affected individuals in Palau, specifically 15q11.2 and 1q21.1 deletions, partial duplication of IL1RAPL1 (Xp21.3), and chromosome X duplications (Klinefelter's syndrome). Partial duplication within A2BP1 appears to convey an eightfold increased risk in male subjects (95% confidence interval, .8-84.4) but not female subjects (odds ratio = .4, 95% confidence interval, .03-4.9). Affected-only linkage analysis using this variant yields a logarithm of the odds score of 3.5.
  
  
  CONCLUSIONS
  This study reveals CNVs that confer risk to schizophrenia and related psychotic disorders in Palau, most of which have been previously observed in samples of European ancestry. Only a few of these CNVs show evidence that they have existed for many generations, consistent with risk variants diminishing reproductive success.
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors: Nadine
authors: N
authors: Melhem
authors: Frank
authors: F
authors: Middleton
authors: Kathryn
authors: K
authors: McFadden
authors: Lambertus
authors: L
authors: Klei
authors: Stephen V
authors: SV
authors: Faraone
authors: Sophia
authors: S
authors: Vinogradov
authors: Josepha
authors: J
authors: Tiobech
authors: Victor
authors: V
authors: Yano
authors: Stevenson
authors: S
authors: Kuartei
authors: Kathryn
authors: K
authors: Roeder
authors: William
authors: W
authors: Byerley
authors: Bernie
authors: B
authors: Devlin
authors: Marina
authors: M
authors: Myles-Worsley
mesh_terms: D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics*; D019029:Palau; D010375:Pedigree; D011618:Psychotic Disorders / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012016:Reference Values; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*