A gene thought to be involved in nerve development can double the risk of schizophrenia when it is damaged, according to a pioneering study into one of most costly mental illnesses.
The findings are further evidence of a genetic basis for schizophrenia – which affects about one in every 100 people at some time of their lives – and could lead to a greater understanding of the physical faults that might lead to the psychiatric disorder in some susceptible people.
The chronic, long-term illness, which results in persistent delusions and hallucinations, is estimated to cost the NHS about £2bn a year in care and treatment alone. But the extra burden on patients, their families and the criminal justice system is thought to be at least twice as high.
Scientists said the genetic fault they have discovered is also associated with a separate inherited disorder that results in learning difficulties and autism. This link, they said, is probably the result of them sharing a common biological pathway at the genetic level.
The gene linked to schizophrenia, called TOP3B, is normally involved in unwinding the DNA double helix to allow other genes to function, especially when the nerve cells of the brain are developing, both in the womb and during the crucial first years of life.
If someone is missing one of the two versions of the gene they inherit from their parents then they run a substantially higher risk of developing schizophrenia than the rest of the population, said Aarno Palotie of the Wellcome Trust Sanger Institute in Cambridge.
“We’ve found that if one gene is missing it causes twice the risk of schizophrenia, but if both are missing then all these people either have severe schizophrenia or severe learning disabilities,” said Dr Palotie, who led the study.
“This is a tremendous discovery for our team. Not only have we uncovered vital information about the biology behind schizophrenia, but we have also linked this same biological process to a disorder associated with learning difficulties,” he said.
“Our findings offer great hope for future studies into the genetic basis of schizophrenia and other brain disorders, potentially finding new drug targets against them,” he added.
The study, published in the journal Nature Neuroscience, was based on an extensive analysis of an isolated population in the municipality of Kuusamo in north-east Finland, where the prevalence of schizophrenia is about three times higher than the rest of the country. Genome scans for single genetic faults led to the discovery that faulty or missing versions of the TOP3B gene were linked with an increased risk of the mental disorder.
The analysis also revealed a link with fragile-X syndrome, an inherited disorder associated with autism.
However, although there is a strong genetic component to schizophrenia – accounting for perhaps 80 per cent of the risk – the disorder is also influenced by upbringing and environment, which probably interact with genetic predispositions.