A genome wide survey supports the involvement of large copy number variants in schizophrenia with and without intellectual disability

Derks, Eske M., Ayub, Muhammad, Chambert, Kimberly, Del Favero, Jurgen, Johnstone, Mandy, Macgregor, Stuart, Maclean, Alan, McKechanie, Andrew G., McRae, Allan F., Moran, Jennifer L., Pickard, Benjamin S., Purcell, Shaun, Sklar, Pamela, St Clair, David M., Wray, Naomi R., Visscher, Peter M. and Blackwood, Douglas H. R. (2013) A genome wide survey supports the involvement of large copy number variants in schizophrenia with and without intellectual disability. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 162 8: 847-854. doi:10.1002/ajmg.b.32189


Author Derks, Eske M.
Ayub, Muhammad
Chambert, Kimberly
Del Favero, Jurgen
Johnstone, Mandy
Macgregor, Stuart
Maclean, Alan
McKechanie, Andrew G.
McRae, Allan F.
Moran, Jennifer L.
Pickard, Benjamin S.
Purcell, Shaun
Sklar, Pamela
St Clair, David M.
Wray, Naomi R.
Visscher, Peter M.
Blackwood, Douglas H. R.
Title A genome wide survey supports the involvement of large copy number variants in schizophrenia with and without intellectual disability
Journal name American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics   Check publisher's open access policy
ISSN 1552-4841
1552-485X
Publication date 2013-12
Sub-type Article (original research)
DOI 10.1002/ajmg.b.32189
Volume 162
Issue 8
Start page 847
End page 854
Total pages 8
Place of publication Hoboken, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
Formatted abstract
Background Copy number variants (CNVs) have been shown to play a role in schizophrenia and intellectual disability.

Methods We compared the CNV burden in 66 patients with intellectual disability and no symptoms of psychosis (ID-only) with the burden in 64 patients with intellectual disability and schizophrenia (ID + SCZ). Samples were genotyped on three plates by the Broad Institute using the Affymetrix 6.0 array.

Results For CNVs larger than 100 kb, there was no difference in the CNV burden of ID-only and ID + SCZ. In contrast, the number of duplications larger than 1 Mb was increased in ID + SCZ compared to ID-only. We detected seven large duplications and two large deletions at chromosome 15q11.2 (18.5–20.1 Mb) which were all present in patients with ID + SCZ. The involvement of this region in schizophrenia was confirmed in Scottish samples from the ISC study (N = 2,114; 1,130 cases and 984 controls). Finally, one of the patients with schizophrenia and low IQ carrying a duplication at 15q11.2, is a member of a previously described pedigree with multiple cases of mild intellectual disability, schizophrenia, hearing impairment, retinitis pigmentosa and cataracts. DNA samples were available for 11 members of this family and the duplication was present in all 10 affected individuals and was absent in an unaffected individual.

Conclusions Duplications at 15q11.2 (18.5–20.1 Mb) are highly prevalent in a severe group of patients characterized by intellectual disability and comorbid schizophrenia. It is also associated with a phenotype that includes schizophrenia, low IQ, hearing and visual impairments resembling the spectrum of symptoms described in “ciliopathies.”
Keyword Schizophrenia
Intellectual disability
Copy number variants
Genetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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Created: Mon, 20 Jan 2014, 10:26:54 EST by Debra McMurtrie on behalf of Queensland Brain Institute