Genetic link between schizophrenia and bi-polar discovered

Despite recent grumbles about their efficacy, genome-wide association studies (GWAS) continue to deliver more and more insights into the genetic components to a number of complex traits and diseases.

The latest disorders to be analysed are schizophrenia and bi-polar disorder, with a global consortium of researchers finding several loci that appear to be involved in both mental illnesses.

The study was the largest ever of these mental illnesses, and involved over 12,000 individuals with either schizophrenia or bi-polar along with 52,000 controls.

It found 11 regions that have strong association with these disorders, including six novel regions that had not been previously observed. Many of the regions were found to be common to both schizophrenia and bi-polar, suggesting some common underlying causes.

One region that appeared in both patient groups was CACNA1C, which is a gene that is important in the calcium channel, involved in cell signalling. Another novel gene involved in cell surface signalling, ODZ4, was also revealed.

“Both findings were highly statistically significant and the research indicates new targets for the development of improved treatments for this severe and disabling condition,” said Scientia Professor Philip Mitchell, Head of the School of Psychiatry at the University of New South Wales (UNSW), and a study author.

“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.”

Another region was associated with a microRNA known to play a role in neuronal development. All of these suggest that both disorders have some underlying genetic causes that are involved in neuronal and brain development and signalling, as well as immune function.

“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,” said Professor Vaughan Carr from UNSW’s School of Psychiatry, and a study author.

The discovery of so many genetic contributing factors to schizophrenia and bi-polar disorder reinforce the notion that the two are somehow related, and that genetics play a significant role in the development of the disorders.

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.

Revealing the genetic components can allow researchers to investigate the causal mechanisms at play in both disorder, such as by looking at how various signalling pathways operate and how they may malfunction in the case of schizophrenia or bi-polar. This, in turn, may lead to new treatments that alter the function of those pathways, returning them to normal.

The studies, which were published in two papers in Nature Genetics, were conducted by the Psychiatric Genome-Wide Association Study Consortium (PGC), which was formed in 2007 and is the largest consortium ever in psychiatry.

The schizophrenia and bi-polar papers were published today in Nature Genetics.