Human Molecular Genetics Advance Access published online on January 29, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp043
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Support for the involvement of large cnvs in the pathogenesis of schizophrenia
Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK
* Corresponding author: Department of Psychological Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK, Tel: +44 29 20687065, Fax: +44 29 20687068, e-mail: owenmj{at}cardiff.ac.uk
Received December 1, 2008; Revised January 14, 2009; Accepted January 21, 2009
We investigated the involvement of rare (< 1%) CNVs in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip® 500K Mapping Array. Large CNVs >1Mb were 2.26 times more common in cases (p=0.00027), with the effect coming mostly from deletions (OR=4.53, p=0.00013) although duplications were also more common (OR=1.71, p=0.04). Two 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 14,0-15,4Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies (HNPP). The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36092 (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=5x10–5. One large duplication on 16p13.1, that has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% vs 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.
** Full list of contributors in these consortia is presented in "Supplementary File Authors"
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