Support for the involvement of large copy number variants in the pathogenesis of schizophrenia

Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Grozeva, Detelina ORCID: https://orcid.org/0000-0003-3239-8415, Norton, Nadine ORCID: https://orcid.org/0000-0002-3848-4288, Ivanov, Dobril ORCID: https://orcid.org/0000-0001-6271-6301, Mantripragada, Kiran Kumar ORCID: https://orcid.org/0000-0003-2070-8105, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 2009. Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Human Molecular Genetics 18 (8) , pp. 1497-1503. 10.1093/hmg/ddp043

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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 × 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Oxford University Press
ISSN:	0964-6906
Date of Acceptance:	21 January 2009
Last Modified:	05 Jan 2024 04:41
URI:	https://orca.cardiff.ac.uk/id/eprint/25799

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