期刊
NATURE
卷 455, 期 7210, 页码 237-241出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature07239
关键词
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资金
- Medical Research Council (UK) Programme
- National Institutes of Mental Health (USA) [CONTE: 2 P50 MH066392-05A1]
- Swedish Council for Working Life and Social Research [FO 184/2000
- 2001-2368]
- Stanley Medical Research Institute [MH071681]
- Narsad Young Investigator Award
- Australian National Health and Medical Research Council
- Science Foundation Ireland
- Health Research Board (Ireland)
- Stanley Medical Research Institute
- Wellcome Trust
- GlaxoSmithKline
- Generation Scotland
- Genetics Health Initiative
- Neuroscience Research Charitable Trust
- Camden and Islington Mental Health and Social Care Trust
- East London and City Mental Heath Trust
- West Berkshire NHS Trust,
- West London Mental Health Trust
- Oxfordshire and Buckinghamshire Mental Health Partnership NHS Trust
- South Essex Partnership NHS Foundation Trust
- Gloucestershire Partnership NHS Foundation Trust
- Mersey Care NHS Trust
- Hampshire Partnership NHS Trust
- North East London Mental Health Trust
- Chief Scientist Office of the Scottish Executive
- Sylvan C. Herman Foundation
- National Institutes of Mental Health and the Department of Veterans Affairs
- [MH074027]
- [MH077139]
- [MH080403]
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(2-7) and also in neurodevelopmental disorders(8-11), 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(12). 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.
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