Working alongside teams from leading research institutions including the Icahn School of Medicine at Mount Sinai, New York, the Broad Institute of the Massachusetts Institute of Technology (MIT), Harvard, and Cambridge Universities, they examined DNA blood samples from 623 sufferers and their parents.
The study showed that "de novo" mutations, which are found in affected individuals but not their parents, play a role in triggering the disorder but more importantly that they preferentially disrupt specific sets of proteins which have related functions in the brain.
These pathways are involved in modulating the strength of connections between nerve cells and play important roles in brain development, learning, memory and cognition.
"We already had evidence from previous work in Cardiff supporting the importance of these pathways but the new findings, together with those from another study published in the same issue of Nature, confirm the importance of these and related sets of proteins," according to Professor Mike Owen from Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics, who co-led the research.
"This degree of convergence from several studies is unprecedented in schizophrenia genetics and tells us that for the first time we have a handle on one of the core brain processes that is disrupted in the disorder," he adds.
As well as identifying how genetic mutations impact on brain function the findings also indicate an overlap with the causes of other neurodevelopmental disorders including autism and intellectual disability.
Professor Mick O'Donovan from Cardiff University's MRC Centre, who jointly led the research added: "The fact we've been able to identify a degree of overlap between the underlying causes of schizophrenia and those in autism and intellectual disability suggests that these disorders might share some common mechanisms and lends further weight to calls for research that integrates findings across multiple disorders.
"We need research that takes into account genetics, cognitive science, imaging and other sources of information rather than relying solely on clinical definitions for psychiatric disorders."
Professor Hugh Perry, Chair of the MRC Neurosciences and Mental Health Board said: "Understanding how our genetic code contributes to Schizophrenia is crucial if we are to develop better, safer treatments. This study adds a body of rapidly emerging research being funded by the Medical Research Council on the role of the genome in mental illness. Such advances in developmental biology will help us to unravel the complexity of emotional and behavioural disturbances."