A single defective gene increases the risk of schizophrenia 35 times and is involved in a range of neurodevelopmental disorders, research has shown.
Although the mutation is very rare, affecting less than one in 1,000 people with the illness, the discovery may lead to a better understanding of psychosis and potential treatments, say scientists.
It is the first time changes to the DNA code of one gene have been so strongly linked to schizophrenia, a severe mental condition affecting nearly 300,000 people in the UK.
Schizophrenia, which usually strikes in the late teens or early 20s, is characterised by symptoms that include hallucinations, delusions, disorganised thinking and dissociation - a feeling of detachment from the outside world.
The disease is also potentially fatal. An estimated 10% - 13% of sufferers kill themselves and around 40% attempt suicide at least once.
Researchers investigating the causes of schizophrenia mapped the complete genetic codes of more than 16,000 people in the UK, Finland and Sweden. They included the genomes of 5,341 individuals who had been diagnosed with the condition.
Damage to one gene, known as SETD1A, was found in 10 of the schizophrenia patients and six other people with developmental and neuropsychiatric disorders such as intellectual disability.
The discovery, reported in the journal Nature Neuroscience, suggests that schizophrenia may share common biological pathways with developmental disorders.
Lead author Dr Jeff Barrett, from the Wellcome Trust Sanger Institute in Hinxton, Cambridgeshire, said: "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.
"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."
Experts are still unsure of what lies at the root of schizophrenia, but previous studies of families have indicated that genes play an important role.
Professor Sir Mike Owen, director of the Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, at the University of Cardiff, said: "We have a very limited understanding of how schizophrenia arises, and this has hampered attempts to develop new treatments.
"Current drugs are only effective in alleviating some of the symptoms, can lead to troubling side effects, and are ineffective in a sizeable minority of cases.
"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."
Brian Dow, from the charity Rethink Mental Illness, said: "Despite affecting around one in 100 of us, schizophrenia remains under-prioritised and misunderstood, particularly when compared to physical health conditions like cancer. Any research that furthers our understanding of the causes of this condition is good news, because what we so often hear from supporters is that they wait years before they get the right treatment and support.
"The next challenge will be applying any new insights to develop desperately needed new treatments, and we need to see further investment in mental health research to make this a reality. This year the Government said it would support more research into mental illnesses, and so we hope to see many more studies like this in the years to come."