title: Support for the involvement of large copy number variants in the pathogenesis of schizophrenia.
abstract: We investigated the involvement of rare (<1%) copy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 x 10(-5). One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.
authors.affiliation: Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Dobril
authors.initials: D
authors.lastname: Ivanov
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Mantripragada
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D006113:United Kingdom