De novo CNVs in bipolar affective disorder and schizophrenia

Georgieva, Lyudmila, Rees, Elliott ORCID: https://orcid.org/0000-0002-6168-9222, Moran, Jennifer L., Chambert, Kimberly D., Milanova, Vihra, Craddock, Nicholas ORCID: https://orcid.org/0000-0003-2171-0610, Purcell, Shaun, Sklar, Pamela, McCarroll, Steven, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, 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. De novo CNVs in bipolar affective disorder and schizophrenia. Human Molecular Genetics 23 (24) , pp. 6677-6683. 10.1093/hmg/ddu379

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Abstract

An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. Copy number variants were called by PennCNV and filtered for frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining results with previous studies and using a cut-off of >100 kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448 kb) was also intermediate between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ. Patients with a positive family history can also harbour de novo 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) Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher:	Oxford University Press
ISSN:	0964-6906
Funders:	MRC, Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	17 July 2014
Last Modified:	07 Jun 2023 19:15
URI:	https://orca.cardiff.ac.uk/id/eprint/63713

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