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Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search longchamp Bags for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs longchamp Sydney by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia longchamp Le Pliage and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.Comment inHuman disease: chipping away at psychiatric disorders. [Nat Rev Genet. 2008]Human Longchamp Australia disease: chipping away at psychiatric disorders.Gunter C. Nat Rev Genet. 2008 Sep; 9(9):654. Schizophrenia: Incriminating genomic evidence. [Nature. 2008]Schizophrenia: Incriminating genomic evidence.Lupski JR. Nature. 2008 Sep 11; 455(7210):178-9.

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