Large-scale genetic studies provide insight into causes of schizophrenia
31 July 2008
Schizophrenia is a mental disorder that typically causes hallucinations, delusions, impairment of cognitive function and apathy. Scientists have known for some time that genetics plays a role in the disorder, but demonstrating robust genetic associations has until now proved difficult.
In two separate papers, the International Schizophrenia Consortium and the SGENE consortium have both identified two rare deletions, one on chromosome 1 and another on chromosome 15, found in around one per cent of people with schizophrenia. In addition, the SGENE team has identified a third deletion, also on chromosome 15.
CNVs have been identified in individual patients with schizophrenia and in patients with brain disorders such as autism before, but until now large-scale genome-wide studies have not been used to explore their role.
Dr Pamela Sklar from Massachusetts General Hospital, Boston, who is part of the International Schizophrenia Consortium, says the findings give hope to people with schizophrenia as well as their friends and family that scientists are moving towards understanding the causes of the disease.
"Of course, this is really the beginning and so much more needs to be done to understand how [these variants] produce disease," says Dr Sklar. "We've only explained a tiny fraction of why people might develop schizophrenia and much more work needs to be done to connect specific changes to the full spectrum of other types of genetic factors that might influence schizophrenia as well as the way in which those might interact with the environment."
In a separate, genome-wide association study funded by the Wellcome Trust and Medical Research Council, a team at Cardiff University - led by Professor Michael O'Donovan - has identified a number of potential genetic candidates. The most strongly associated of these is a common variant near the gene ZNF804A, which regulates expression of other genes.
"[Our study] means that all of us or virtually all of us have some genes for schizophrenia and there are probably hundreds of them," says Professor O'Donovan. "Those of us that don't have the disease probably don't have enough of the genes or possibly have not been exposed to the right environment."
Professor O'Donovan hopes that the findings will be important in helping reduce stigma towards the disease.
"People with schizophrenia are amongst the most rejected and stigmatised in society and the same is true of their families who have often in history been blamed for actually causing the disorder," says Professor O'Donovan. "Hopefully by showing that schizophrenia is a disorder that can be studied and understood in more conventional terms, the three studies reported today will make some small contribution to a long-overdue shift in how this most human of disorders is perceived."
Image: Schizophrenia – hearing voices, illustration by Adrian Cousins, Wellcome Images
References
The International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature, 31 July 2008; DOI: 10.1038/nature07239
Stefansson H et al. Large recurrent microdeletions associated with schizophrenia. Nature, 31 July 2008; DOI: 10.1038/nature07229
O'Donovan M et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics, E-published ahead of print 31 July 2008; DOI: 10.1038/ng201