Trinity College Researchers Contribute to New Findings in Largest International Genomics Studies of Schizophrenia and Bipolar Disorder

Posted on: 29 September 2011

An international research consortium, including researchers from Trinity College Dublin, has discovered that common genetic variants contribute to a person’s risk of schizophrenia and bipolar disorder.  These studies, provide new evidence that 11 regions of the genome have strong, confirmed association with these diseases.  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 recently published online in two papers in the prestigious journal Nature Genetics, represent significant advances in the understanding of the causes of these chronic and often debilitating disorders.  Research on schizophrenia and bipolar disorder by the Psychosis Research Group at TCD is funded by Science Foundation Ireland, the Health Research Board and the Wellcome Trust.

“These two large studies, which included participation by more than  4,000 Irish people,  represent a significant step forward for our field.  They offer promising insights into the underlying biology of the risk genes,” says Science Foundation Ireland Principal Investigator, Prof Aiden Corvin, Head of the Psychosis Research Group at Trinity College Dublin and one of several co-authors from Psychiatry at Trinity College.

“In the case of the schizophrenia findings, we found five new genes which are linked with the disorder.  Perhaps the most significant finding was that one of these genes seems to act as a type of master key with the potential to control about three hundred other genes. This is likely to be the key to a genetic network of hundreds of genes which regulate the development of neurons in the brain. Understanding and targeting this process may open up new molecular targets for the treatment of schizophrenia.”

“The work in bipolar disorder is already prompting new research into the role of calcium channel receptors in mood regulation.  We discovered that several of the risk genes involved in bipolar disorder are involved in regulating the function of calcium channels.  Several existing treatments were known to regulate calcium channel function, but the importance of this was uncertain.  These new findings bring calcium regulation into intensive focus in the search for new treatments.”

“This research comes at an exciting time, with parallel discoveries in neuroscience making it increasingly possible to investigate the underlying biological causes of conditions like schizophrenia and bipolar disorder.  Knowing more about the biology is key, as the development of new treatments has stalled over several decades, and these findings provide potentially important new treatment targets,” concluded Prof Corvin who was also a member of the management committee for the project.

Schizophrenia and bipolar disorder are common and often devastating brain disorders.  Some of the most prominent symptoms of schizophrenia are persistent delusions, hallucinations and cognitive problems.  Bipolar disorder (or manic-depressive illness) is characterised by episodes of severe mood problems including mania and depression.  Both affect about1% of the world’s population and usually strike in late adolescence or early adulthood.  Despite the availability of treatments, these illnesses are usually chronic, 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 dozens of genes, along with environmental factors, contribute to disease risk.

Formed in 2007, the Psychiatric Genome-Wide Association Study Consortium 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 bodies including awards from the Health Research Board, Science Foundation Ireland and the Wellcome Trust to the TCD group.  Funds for coordination of the consortium was provided by the US National Institute of Mental Health.

The papers are available at the following links:

Genome-wide association study identifies five new schizophrenia loci.

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.