Major mental illnesses, such as schizophrenia and bipolar disorder, are devastating disorders that place a huge burden on the individual sufferers, their families and society as a whole. It has long been recognised that such disorders are in some way inherited through our genes. Disrupted in Schizophrenia 1 (DISC1) is currently the most compelling candidate gene for major mental illness.
Ever since the gene for DISC1 was discovered in 2000, 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 direct damage to the DISC1 gene increasing risk of major mental illness in a Scottish family, the genetic evidence from other studies has been less clear cut. In collaboration with groups from Edinburgh, Aberdeen, London and Helsinki, I have studied approximately 1,000 cases of schizophrenia and 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, this goes some way to explain the subtle way in which DISC1 affects risk.
From this consistent observation between groups, I studied the affect these variants have at the cellular level. This was carried out using a novel cost effective method, which takes advantage of publicly available data, to compare the presence of these variants with alterations in gene expression, the amount of protein made. Interestingly I found that DISC1 affects a number of other genes that current mental illness medications are designed to target. It is therefore possible that by identifying those patients in whom DISC1 may be a root cause of illness, we could find the patients for whom these drugs would be most effective.
