An international research consortium has confirmed that common genetic variants contribute to a person’s risk of schizophrenia and bipolar disorder.
The largest study of its kind provides new molecular evidence that 11 regions have strong association with these diseases, including six regions not previously observed. The researchers also found that many of these DNA variations contribute to both diseases.
The findings, reported by the Psychiatric Genome-Wide Association Study Consortium (PGC) and published online in two papers in the journal Nature Genetics, represent significant advances in the understanding the causes of these severe and often debilitating disorders.
Scientia Professor Philip Mitchell, Head of the School of Psychiatry at the University of New South Wales (UNSW), and senior researcher at Black Dog Institute and Professor Peter Schofield, Executive Director Neuroscience Research Australia, were involved in the bipolar disorder paper, while Professor Vaughan Carr from UNSW’s School of Psychiatry contributed to the paper on schizophrenia.
Professor Mitchell said: "This is ground-breaking research. The bipolar disorder study involved 12,000 patients and 52,000 controls – the largest ever study of this condition. The research confirmed that a gene for a component of the calcium channel (CACNA1C) is involved in causing bipolar disorder and also identified a novel gene involved in cell surface signaling (ODZ4). Both findings were highly statistically significant and the research indicates new targets for the development of improved treatments for this severe and disabling condition.
"Moreover, when both the bipolar disorder and schizophrenia groups were combined, there was evidence that CACNA1C was involved in both conditions – verifying a number of research strands indicating some genetic overlap between these two disorders."
Professor Schofield said the study was a testimony to international spirit of collaboration between psychiatric genetics researchers from around the world.
"We have shared our data so that together we can make new insights into the biology of bipolar disorder.
"Bipolar is an illness with a strong heritable or genetic component. However, unlike many other genetic disorders, it arises not by mutations or errors in a single gene, but rather by subtle variants in dozens, maybe even thousands of genes. This study shows that an international consensus is beginning to emerge on the beginnings of an understanding of the biology of bipolar disorder."
Professor Vaughan Carr, who is also CEO of the Schizophrenia Research Institute, said a strong new finding was of a genomic region known to regulate neuronal development and which may contribute to developmental brain abnormalities found in schizophrenia.
"Replication is very important in science. The finding that a genomic region associated with histocompatibility has again been confirmed in relation to schizophrenia highlights the potential role of inflammation in the development of schizophrenia and opens up the possibility of new treatments based on immunological processes."
Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms in schizophrenia are persistent delusions, hallucinations and cognitive problems. Bipolar disorder (or manic-depressive illness) is characterized by episodes of severe mood problems including mania and depression. Both usually strike in late adolescence or early adulthood.
Despite the availability of treatments, these illnesses are either chronic or recurrent, and response to treatment is often incomplete leading to prolonged disability and personal suffering. Family history, which reflects genetic inheritance, is a strong risk factor for both schizophrenia and bipolar disorder, and it has generally been assumed that many genes, along with environmental factors, contribute to disease risk.
Formed in 2007, the PGC is the largest consortium ever in psychiatry. Over 250 researchers from more than 20 countries have come together in an unparalleled spirit of cooperation to advance knowledge of the genetic causes of mental illness. Crucial to the success of the project was the willingness of many groups to share genetic data from tens of thousands of patients collected over many years.
The research was funded by numerous European, US, and Australian funding bodies. Funding to coordinate the consortium was provided by the US National Institute of Mental Health. The Australian component of this research was supported by the National Health and Medical Research Council.
NeuRA's Dr Jan Fullerton also contributed to this research.