London (ISJ): A team of scientists at Cardiff University have discovered over a hundred genetic risk factors linked to schizophrenia, which provides vital clues for treatment of the disease.
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.
The study published in Nature had examined a total of 80,000 samples from schizophrenia patients and healthy volunteers worldwide, found 108 specific locations in the human genome linked to schizophrenia, 83 of which were entirely new.
“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 24 million 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.
“Although we are very excited by the findings, it is important not to overstate or misinterpret them, said Prof. O’Donovan. “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.?
“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,” hopped Prof. O?Donovan.
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Scientists have discovered the cause of sudden cardiac death in young children, for the first time making it possible to pinpoint a therapeutic target for future efforts in developing a cure.
Heart specialists at Cardiff found that incoherent communication between two vital proteins in heart cells was to blame for the previously inexplicable cause of death.
“A healthy and regular heartbeat is maintained by precise control of the calcium level in heart muscle cells, but our experiments have identified a genetic flaw that invites chaos to this process,” said team leader of the study, Professor Tony Lai from the School of Medicine?s Sir Geraint Evans Wales Heart Research Institute (WHRI).
Dr Michail Nomikos, also from the School of Medicine and the study?s lead author, explained why this biological equilibrium becomes unstable: “When calcium levels rise the heart contracts and when the calcium levels drop the heart muscle relaxes, similar to the upstroke and downstroke of a motor engine. The precise control of this movement relies on the direct physical interaction between a calcium channel protein ryanodine receptor (RyR), and a calcium-sensing protein called calmodulin.”
“We discovered that a genetic mutation in calmodulin causes a loss of regular heart rhythm and produces ineffective communication between calmodulin and RyR. Our findings show that there is inadequate binding between these proteins due to the mutated calmodulin gene resulting in the loss of control of cell calcium level and thereby abnormal heart function.
“Abnormal changes in calcium levels disrupt the smooth cycling between cardiac contraction and relaxation that leads to irregular heartbeat and sudden death.”
In the future, Professor Lai anticipates that finding a way to intervene in ensuring a stable interaction between calmodulin and RyR in the heart will give doctors a new weapon in the fight against sudden cardiac death.
Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: “Keeping the heart’s calcium levels under control is critical to maintaining a healthy rhythm.
“By showing how calmodulin mutation could disrupt this and lead to sudden cardiac death, the Cardiff team have provided new clues for how to treat the condition in the future.
“Uncovering genetic links like this is vital to help combat the devastating effects of inherited heart conditions. The BHF is urgently campaigning for more research to help find the undiscovered faulty genes putting people at greater risk of heart disease.”
