De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia

A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de…

• SM
  Stanley Medical Research Institute
• WT
  Wellcome Trust
• BI
  Broad Institute
• EC
  European Commission

  Awards: 218251, 242167, 241995, 223423
• CU
  Cardiff University

  Award: G0800509
• SC
  Stanley Center for Psychiatric Research, Broad Institute
• MR
  Medical Research Council

  Awards: G0800509, MH066392