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


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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.

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