A study of over 11,000 patients with schizophrenia has helped to provide the "strongest evidence yet" of what causes the condition, said Cardiff University scientists.
They have led the biggest study of its kind, comparing patients' genetic data with 16,416 people without the illness.
They said the findings showed how the disruption of a chemical balance in the brain is implicated in the disorder.
The results have been published in the journal Neuron.
Dr Andrew Pocklington from the university's MRC Centre for Neuropsychiatric Genetics and Genomics said: "We're finally starting to understand what goes wrong in schizophrenia.
"A reliable model of the disease is urgently needed to direct future efforts in developing new treatments which haven't really improved a great deal since the 1970s."
A healthy brain functions properly due to a precise balance between chemical signals that excite and inhibit nerve cell activity, the experts explained.
The latest findings build on evidence the team found in 2011 that schizophrenia mutations interfere with that signalling process.
Dr Pocklington said: "Our study marks a significant step towards understanding the biology underpinning schizophrenia which is an incredibly complex condition and has up until very recently kept scientists largely mystified as to its origins."