Schizophrenia: a common disease caused by multiple rare alleles - PubMed (original) (raw)

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Schizophrenia: a common disease caused by multiple rare alleles

Jon M McClellan et al. Br J Psychiatry. 2007 Mar.

Abstract

Schizophrenia is widely held to stem from the combined effects of multiple common polymorphisms, each with a small impact on disease risk. We suggest an alternative view: that schizophrenia is highly heterogeneous genetically and that many predisposing mutations are highly penetrant and individually rare, even specific to single cases or families. This "common disease--rare alleles" hypothesis is supported by recent findings in human genomics and by allelic and locus heterogeneity for other complex traits. We review the implications of this model for gene discovery research in schizophrenia.

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Comment in

• Phenotypic and genetic complexity of psychosis. Invited commentary on ... Schizophrenia: a common disease caused by multiple rare alleles.
  Craddock N, O'Donovan MC, Owen MJ. Craddock N, et al. Br J Psychiatry. 2007 Mar;190:200-3. doi: 10.1192/bjp.bp.106.033761. Br J Psychiatry. 2007. PMID: 17329738
• Genetic hypotheses for schizophrenia.
  Crow T. Crow T. Br J Psychiatry. 2007 Aug;191:180; author reply 180-1. doi: 10.1192/bjp.191.2.180. Br J Psychiatry. 2007. PMID: 17666506 No abstract available.

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