Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: Risk and transmission in extended pedigrees

Nadine Melhem, Frank Middleton, Kathryn McFadden, Lambertus Klei, Stephen V. Faraone, Sophia Vinogradov, Josepha Tiobech, Victor Yano, Stevenson Kuartei, Kathryn Roeder, William Byerley, Bernie Devlin, Marina Myles-Worsley

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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,.884.4) but not female subjects (odds ratio =.4, 95% confidence interval,.034.9). 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.

Original languageEnglish (US)
Pages (from-to)1115-1121
Number of pages7
JournalBiological psychiatry
Issue number12
StatePublished - Dec 15 2011
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to the people of Palau for their participation in this study. For short tandem repeat and Y marker results, genotyping services were provided by the Center for Inherited Disease Research. The Center for Inherited Disease Research is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C .

Funding Information:
In the past year, Dr. Faraone received consulting fees and was on Advisory Boards for Shire Development and received research support from Shire and the NIH. In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. In previous years, he received research support from Eli Lilly, Shire, Pfizer, and the NIH. Dr. Faraone receives royalties from a book published by Guilford Press, Straight Talk About Your Child's Mental Health. All other authors report no biomedical financial interests or potential conflicts of interest.

Funding Information:
This study was supported by National Institutes of Health (NIH) Grants MH080375 , MH080373 , MH080299 , and MH077930 .


  • A2BP1
  • IL1RAPL1
  • Palau
  • copy number variants (CNVs)
  • psychotic disorders
  • schizophrenia


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