Analysis of copy number variations at 15 schizophrenia-associated loci

Rees, Elliott ORCID: https://orcid.org/0000-0002-6168-9222, Walters, James T. R. ORCID: https://orcid.org/0000-0002-6980-4053, Georgieva, Lyudmila, Isles, Anthony R. ORCID: https://orcid.org/0000-0002-7587-5712, Chambert, Kimberley D., Richards, Alexander L., Mahoney-Davies, Gerwyn, Legge, Sophie E., Moran, Jennifer L., McCarroll, Stephen A., O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862 and Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950 2014. Analysis of copy number variations at 15 schizophrenia-associated loci. British Journal of Psychiatry 204 (2) , pp. 108-114. 10.1192/bjp.bp.113.131052

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Abstract

Background: A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain. Aims: To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies. Method: We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets. Results: We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10–4). Conclusions: We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Cambridge University Press
ISSN:	0007-1250
Funders:	Medical Research Council (MRC) Centre (G0800509) and Program Grants (G0801418), European Community's Seventh Framework Programme (HEALTH-F2-2010-241909 (Project EU-GEI), MRC PhD Studentship to E. Rees
Date of First Compliant Deposit:	30 March 2016
Last Modified:	12 Oct 2023 04:40
URI:	https://orca.cardiff.ac.uk/id/eprint/57364

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