The mutation was found in the SETD1A gene, which occurs in less than one in 1000 people with the disorder. The finding may provide insight into the biological causes of schizophrenia as well as other developmental and psychiatric disorders.
'The results were surprising, not only that we found such a high level of certainty that the SETD1A gene was involved, but also that the effects of the gene were so large,' said Dr Jeff Barrett, lead author of the study and group leader at the Wellcome Trust Sanger Institute.
'Psychiatric disorders are complex diseases involving many genes and it is extremely difficult to find conclusive proof of the importance of a single gene. This is a really exciting finding for research into schizophrenia.'
Dr Barrett's team examined gene sequence in 4,264 people with schizophrenia and 9,343 healthy controls in the UK, Finland and Sweden. Their aim was to identify possible rare and alternative gene variants in people with schizophrenia, investigating the most potentially disruptive across the entire genome.
The study, published in Nature Neuroscience, the group identified a strong association between schizophrenia and a mutation in the SETD1A gene. This mutation, present in only ten participants in the study, was associated with an increased risk of schizophrenia of 35 times. Seven of those with the SETD1A mutation also demonstrated learning difficulties, and the same rare variant was also found in some children with developmental problems and adults with other neuropsychiatric disorders.
'Defects in the SETD1A gene, which by itself explains only a small fraction of cases, may guide us towards new pathways that could be targets for therapeutic drugs in a larger number of cases,' said Professor Mike Owen, Director of Cardiff University's MRC Centre for Neuropsychiatric Genetic and Genomics and a co-author of the study.
Schizophrenia affects 300,000 people in the UK and, while its causes are uncertain, studies show that a predisposition to the disorder can run in families.
The researchers say that this particular mutation could affect brain development more generally, and schizophrenia may share biological pathways – and ultimately potential therapeutic targets – with other neuropsychiatric and developmental disorders.
Professor John McGrath, from the Queensland Brain Institute at the University of Queensland, who was not involved in the study, told ABC Online that it was a very significant discovery. 'The most common disorders have a mix of genetic factors and environmental factors. Some of these things are modifiable, but the genetic factors are always there and we're trying to join the dots to explain why some people go on to get the illness,' he said. 'This new finding has given us a big new clue to track down what may underlie some types of schizophrenia.'