An international team of researchers has found that the cause of schizophrenia is even more complex than already believed, with rare gene mutations contributing to the disorder. In two studies published in the journal Nature, they show that schizophrenia arises from the combined effects of many genes.
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Blood DNA taken from 6,948 people in Bulgaria and Sweden was catalogued. This included patients diagnosed with schizophrenia, their parents and healthy controls. Scientists were able to pinpoint the sites of gene mutations and identify patterns that reveal clues about the biology underlying schizophrenia. Rather than finding only a few "faulty" genes, the two studies determine that the genetic basis of schizophrenia is tremendously complex. The data confirms that it is a very large number of rare genetic mutations that contribute to risk of developing the disorder.
Schizophrenia is a chronic, often debilitating mental illness that affects 1% of people at some time in their lives. Symptoms include persistent hallucinations, delusions and paranoia. The exact cause of the disorder remains unknown, but is considered to result from a complex interplay of a person's genes and their environment.
Many studies have shown that schizophrenia runs in families and so genes are undoubtedly a factor. A tenth of people with schizophrenia have a parent with the condition. But, despite its high heritability, a large number of individuals with schizophrenia do not have a family history of the disease. The search for a "schizophrenia gene", though popular, has not proved fruitful. This research sheds light on how genetics plays a role in cases which have not been inherited.
These two new studies are the result of the largest genetic study of its kind with scientists hailing from nine different institutions including Cardiff University and the Broad Institute of MIT and Harvard. The clinical and genetic information gathered on more than 3,000 affected individuals has produced the world's largest database on schizophrenia.
Technological improvements enabled researchers to sequence and examine the components of genes and they detected changes at the scale of single nucleotides. Despite the large sample size, no individual gene could be conclusively identified as the culprit for causing schizophrenia.
But a new window was found into the disorder in the study led by Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics. They examined the role of new mutations – those that are found in affected individuals, but not their parents. These mutations account for roughly 5% of schizophrenia cases.
Michael O'Donovan who co-led this research said, "looking for individual changes to the chemical composition of genes, we found what we predicted. Even small new mutations were not randomly occurring, but were concentrated in a relatively small number of genes that are crucial to the way nerve cells communicate across synapses."
Their research showed that mutations found in affected individuals, but not their parents, disrupt specific sets of proteins. It focused on analyzing the protein-coding regions of people's DNA and identified how these mutations play a role in triggering the disorder. They preferentially disrupt specific sets of proteins which have related functions in the brain.
Other layers of data are now needed to build a fuller picture that will enable researchers to start thinking of new ways to treat patients. Elizabeth Tunbridge, research fellow in Psychiatry at Oxford University, said that developing treatment is still a long way off. But the research is "reassuringly consistent with existing research [into schizophrenia]."
This research also shows that the new mutations cluster in the same way in those who have inherited the disease. This confirms that schizophrenia is inherently the same however it develops.