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22 July 2014
The discovery of over a hundred genetic risk factors linked to schizophrenia provides vital new clues in understanding what causes the condition and will kick-start the search for new treatments, according to University scientists.
In the biggest molecular genetic study of schizophrenia ever conducted, the Psychiatric Genetics Consortium (PGC), led by Professor Michael O’Donovan from the University’s MRC Centre for Neuropsychiatric Genetics and Genomics, combined all available schizophrenia samples into a new, single systematic analysis.
The study is the result of several years of work by the Schizophrenia Working Group of the Psychiatric Genomics Consortium, an international, multi-institutional collaboration of over 300 scientists in 35 countries worldwide.
"We’ve been able to detect genetic risk factors on a huge and unprecedented scale and shed new light on the biological cause of the condition," according to Professor O’Donovan, who led the study.
Examining a total of 80,000 samples from schizophrenia patients and healthy volunteers worldwide the study, published in Nature, found 108 specific locations in the human genome linked to schizophrenia, 83 of which were entirely new.
The new findings also point to new biological mechanisms and pathways.
For example, as the authors had expected, the study implicates genes expressed in brain tissue but it also found genes associated with schizophrenia were particularly active in the immune system.
"These remarkable findings were only made possible through a global collaboration," according to Professor Sir Mike Owen, Director of Cardiff University’s MRC Centre for Neuropsychiatric Genetics and Genomics.
"Detecting biological risk factors on this scale shows that schizophrenia can be tackled by the same approaches that have already transformed outcomes for people with other diseases.
"We now believe they can also do so for schizophrenia which has, until now, been so poorly understood," he added.
Schizophrenia is a debilitating psychiatric disorder that affects more than 24M people worldwide.
The disorder is variable but is characterised by a combination of hallucinations, delusions such as paranoia, mood changes, apathy and social withdrawal amongst others, and often emerges in the teens and early 20s.
Its lifetime impact on individuals and society is high, both in terms of years of healthy life lost to disability and in terms of financial cost.
Many respond well to treatment but, for a large number who do not respond the options are limited, largely because the biological mechanisms underlying schizophrenia have not been understood.
Professor O’Donovan now hopes the wealth of new findings will help kick-start the search for new treatments
He added: "Although we are very excited by the findings, it is important not to overstate or misinterpret them.
"We are still in the early days of trying to understand what causes the disease, however collaborations like this and new genetic tools mean we find ourselves in a unique position.
"Reaping the full benefits of this research for treatment will be a medium to long game but since some of our findings point to already known targets for existing treatments, it is reasonable to hope that others might similarly do in a shorter time frame.
"The wealth of new findings provides a huge number of launch pads for understanding the disease and will kick-start the stalled process of developing new treatments for patients and their families who are even now still stigmatised and blamed for the condition.
"The key challenge now is to translate these new insights into the biological basis of schizophrenia, into new diagnostic tools and novel treatments for patients and finally put an end to the 60-year-wait for new treatments for sufferers worldwide."
Psychiatric Genetics Consortium
MRC Centre for Neuropsychiatric Genetics and Genomics
Neuroscience and Mental Health Research Institute
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