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Common genetic risk factors for major psychiatric disorders uncovered

02 July 2009

Scientists from the MRC Centre for Neuropsychiatric Genetics and Genomics at the University, which was launched today by the First Minister for Wales, Rhodri Morgan, are part of an international research team that has discovered that most of the genetic basis of schizophrenia comes from the accumulation of small effects from thousands of common genetic variants. Many of these genetic effects are also shared by individuals with bipolar disorder.

In a novel use of genome chip data, the International Schizophrenia Consortium found thousands of genetic variants had small influences separately but together make a strong impact on a person’s risk for developing schizophrenia and bipolar disorder, in a report published online today by the journal Nature.

Michael O'Donovan, Professor of Psychiatric Genetics at the MRC Centre for Neuropsychiatric Genetics and Genomics, part of the School of Medicine, said: "The very large number of genetic contributions surprised us initially yet we observed the same pattern across multiple samples, making us confident that we were measuring something real and relevant."

Schizophrenia is a common, chronic and often devastating brain disorder characterised by persistent delusions and hallucinations. It affects about one person in 100 and usually strikes in late adolescence or early adulthood.

Despite the availability of effective treatments, the course of the illness is usually chronic and response to treatments is often limited, leading to prolonged disability and personal suffering. Family history, which signifies genetic inheritance, is a strong risk factor for schizophrenia and bipolar disorder. Last year, the International Schizophrenia Consortium found that rare chromosomal deletions and duplications of all types elevate risk of developing schizophrenia.

Formed in 2006, the International Schizophrenia Consortium is led by senior researchers from 11 institutes in Europe and the USA. Crucial to the success of the project was the willingness of Consortium groups to pool DNA resources that has taken them years to collect, totaling 3,391 individuals with schizophrenia and 3,181 related individuals without the disorder.

The investigators used new genomic technologies and novel analytical techniques. Based upon the theoretical models of Consortium members Drs. Naomi Wray and Peter Visscher (Queensland Institute of Medical Research, Brisbane, Australia), the Consortium tested hundreds of thousands of genetic variants to find those more common in patients with schizophrenia than in people without the disorder.

They then went on to test a subset of about 30,000 of these variants in additional people with schizophrenia and also in people with bipolar disorder. The critical finding was that the same large group of genetic variants was found in the new samples of schizophrenia patients, even when they were collected by many different investigators and tested in different laboratories.

Surprisingly, this group of schizophrenia-related variants was also more common in people with bipolar disorder. These results are at odds with the orthodoxy in psychiatry that the two disorders are distinct. The finding was relatively specific to psychiatric disorders rather than general illness, since the variants were not found in excess in people with a range of other diseases such as diabetes and heart disease.

Eric Lander, founding director of Consortium partner The Broad Institute, and a member of the President Obama’s Council of Advisors on Science and Technology said: "Over the past year, using techniques designed to study common DNA changes, psychiatric disease geneticists have detected more statistically compelling findings than in the previous 100 years."

Dr Thomas Insel, director of the National Institute for Mental Health, which partially funded the study, said: "If some of the same genetic risks underlie schizophrenia and bipolar disorder, perhaps these disorders originate from some common vulnerability in brain development. Of course the big question then is how some people develop schizophrenia and others develop bipolar disorder."

Professor Ian Hickie, Executive Director of the Brain and Mind Institute, University of Sydney, Australia said: "This is a key study from both a conceptual and a practical perspective. It provides striking evidence for the common genetic risk factors for the major psychiatric disorders. We are well on the way to dismantling the century-old classification systems in psychiatry that have proved to be poor representations of the underlying biology."

The study was supported by grants from the Medical Research Council, Wellcome Trust, Science Foundation Ireland, Stanley Medical Research Foundation, the National Institute of Mental Health and the Sylvan Herman Foundation.

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