Rare chromosomal deletions and duplications increase risk of schizophrenia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09-11

AUTHORS

Jennifer L. Stone, Michael C. O’Donovan, Hugh Gurling, George K. Kirov, Douglas H. R. Blackwood, Aiden Corvin, Nick J. Craddock, Michael Gill, Christina M. Hultman, Paul Lichtenstein, Andrew McQuillin, Carlos N. Pato, Douglas M. Ruderfer, Michael J. Owen, David St Clair, Patrick F. Sullivan, Pamela Sklar, Shaun M. Purcell (Leader), Jennifer L. Stone, Douglas M. Ruderfer, Joshua Korn, George K. Kirov, Stuart Macgregor, Andrew McQuillin, Derek W. Morris, Colm T. O’Dushlaine, Mark J. Daly, Peter M. Visscher, Peter A. Holmans, Michael C. O’Donovan, Patrick F. Sullivan, Pamela Sklar, Shaun M. Purcell (Leader), Hugh Gurling, Aiden Corvin, Douglas H. R. Blackwood, Nick J. Craddock, Michael Gill, Christina M. Hultman, George K. Kirov, Paul Lichtenstein, Andrew McQuillin, Michael C. O’Donovan, Michael J. Owen, Carlos N. Pato, Shaun M. Purcell, Edward M. Scolnick, David St Clair, Jennifer L. Stone, Patrick F. Sullivan, Pamela Sklar (Leader), Michael C. O’Donovan, George K. Kirov, Nick J. Craddock, Peter A. Holmans, Nigel M. Williams, Lucy Georgieva, Ivan Nikolov, N. Norton, H. Williams, Draga Toncheva, Vihra Milanova, Michael J. Owen, Christina M. Hultman, Paul Lichtenstein, Emma F. Thelander, Patrick Sullivan, Derek W. Morris, Colm T. O’Dushlaine, Elaine Kenny, John L. Waddington, Michael Gill, Aiden Corvin, Andrew McQuillin, Khalid Choudhury, Susmita Datta, Jonathan Pimm, Srinivasa Thirumalai, Vinay Puri, Robert Krasucki, Jacob Lawrence, Digby Quested, Nicholas Bass, David Curtis, Hugh Gurling, Caroline Crombie, Gillian Fraser, Soh Leh Kwan, Nicholas Walker, David St Clair, Douglas H. R. Blackwood, Walter J. Muir, Kevin A. McGhee, Ben Pickard, Pat Malloy, Alan W. Maclean, Margaret Van Beck, Peter M. Visscher, Stuart Macgregor, Michele T. Pato, Helena Medeiros, Frank Middleton, Celia Carvalho, Christopher Morley, Ayman Fanous, David Conti, James A. Knowles, Carlos Paz Ferreira, Antonio Macedo, M. Helena Azevedo, Carlos N. Pato, Jennifer L. Stone, Douglas M. Ruderfer, Joshua Korn, Steve A. McCarroll, Mark Daly, Shaun M. Purcell, Pamela Sklar, Shaun M. Purcell, Jennifer L. Stone, Kimberly Chambert, Douglas M. Ruderfer, Joshua Korn, Steve A. McCarroll, Casey Gates, Stacey B. Gabriel, Scott Mahon, Kristen Ardlie, Mark J. Daly, Edward M. Scolnick, Pamela Sklar

ABSTRACT

Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73-90% (ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants (CNVs) have been identified in individual patients with schizophrenia and also in neurodevelopmental disorders, but large-scale genome-wide surveys have not been performed. Here we report a genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high-density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15-fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single-occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo-cardio-facial syndrome, which includes psychotic symptoms in 30% of patients. Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome-wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome-wide and at specific loci. More... »

PAGES

237

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature07239

DOI

http://dx.doi.org/10.1038/nature07239

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040865418

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18668038


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