Centre for Molecular Medicine News

New support for DISC1 affecting risk of schizophrenia and Bipolar Disorder

Scientists at the Centre for Molecular Medicine report a new twist to the unfolding story of how DISC1 influences risk of schizophrenia and bipolar disorder, two major forms of mental illness (Hennah et al, Molecular Psychiatry, 4th March, 2008 doi:10.1038/mp.2008.22).

Ever since the gene for DISC1 was discovered in 2000 by scientists at the University of Edinburgh and MRC Human Genetics Unit, evidence has accumulated to indicate that DISC1 plays an important role in how the brain is built, how we build memories and how these processes are affected in major mental illness. But apart from the original report of clear cut damage to the DISC1 gene increasing risk of major mental illness in a large Scottish family, the genetic evidence from other studies, while supporting a general role for DISC1 as a risk factor has been less clear cut.

Now Hennah and colleagues, collaborating with psychiatrists in Aberdeen, London and Helsinki, have studied over 1,000 cases of schizophrenia and slightly fewer cases of bipolar disorder and shown that there are at least three genetic risk variants in the DISC1 gene. Intriguingly, their effects are stronger in combination than individually. These results need to be confirmed by further independent studies. If confirmed, this would go some way to explain the subtle way in which DISC1 affects risk. It may also be a general lesson for other similar genetic studies.

Importantly, this finding only came to light by a very detailed analysis of genetic variation in the DISC1 gene and would have been missed completely by the now common approach of scanning the whole genome to hunt for individual genetic risk factors for other common diseases, such as diabetes, heart disease and cancer. IGMM scientists are working on statistical methods to try to take account of this and can learn useful lessons from our experience working on DISC1.

This article posted 13/3/2008