“Scientists have discovered a gene which may help explain the causes of mental illness,” according to BBC News. The gene, called ABCA13, was reported to be only partially active in patients with schizophrenia, bipolar disorder and depression”.
The news comes from a genetic study which looked at how the gene varied between people with mental health problems and those without. It was estimated that the genetic variants identified could account for about 2% of the risk of schizophrenia and 4% of the risk of bipolar disorder in the general population.
Although these findings may direct future research, there is likely to be a long delay before they lead to the development of drugs, as news coverage has suggested. Psychiatric illnesses are complex and varied, and they are likely to have many contributing factors, both genetic and environmental. Individual studies of this type, while informative, may only provide a small piece of a much larger puzzle.
Where did the story come from?
This research was conducted by Helen Knight, Benjamin Pickard and colleagues from the University of Edinburgh and other research centres in Scotland, Australia and the US. The study was funded by the Wellcome Trust, the Scottish government, Research into Ageing and Help the Aged. The study was published in the peer-reviewed American Journal of Human Genetics.
The Daily Telegraph and BBC News covered this story and generally gave a balanced account. However, the BBC’s headline – “‘Mental illness gene’ discovered by Scots scientists” – may suggest that the gene studied is the sole or primary gene for mental illness. There are likely to be many different genes, as well as environmental factors, that contribute to different psychiatric disorders.
What kind of research was this?
This was a case control study which compared genetic variations of the ABCA13 gene in people with psychiatric illnesses (cases) and people without these disorders (controls). The researchers particularly focused on people with schizophrenia and bipolar disorder.
Psychiatric illnesses are complex and varied, and they are likely to have many contributing factors, both genetic and environmental. There are likely to be multiple genes that contribute to psychiatric illness, and these will vary depending on the illness. Pinpointing the genetic causes helps researchers to understand the biological processes behind these diseases, which may in turn suggest ways to treat them. However, there will probably be a long wait between the discovery of potential contributory factors and the development of new drug treatments.
What did the research involve?
The researchers first studied a 48-year-old man with severe chronic schizophrenia and an abnormal rearrangement of chromosomes. This rearrangement was thought to potentially be the cause of his condition, so the researchers investigated this rearrangement further.
They found that it disrupted the actions of the ABCA13 gene, which had not previously been thought to be associated with psychiatric illness. The gene contains instructions for making the ABCA13 protein, which transports compounds across membranes in the cell. The researchers then ran tests to see whether this gene normally was “switched on” (producing the ABCA13 protein) within the cells of human and mouse brains.
They then looked to see whether this gene might be involved in other cases of schizophrenia and other psychiatric disorders. To do this, they looked for variations in this gene in 1,119 people with schizophrenia, 680 with bipolar disorder (sometimes called manic depression), 365 with depression and 2,270 control participants without these disorders. They also looked for the presence of these genetic variants in the relatives of people with psychiatric illnesses and genetic variations.
The researchers carried out a number of statistical tests to compare cases and controls. Carrying out multiple statistical tests increases the likelihood of finding a significant difference by chance rather than because a true difference exists. The researchers took this into account in their analyses, which was an appropriate step to increase the reliability of their results.
What were the basic results?
The researchers found that the ABCA13 gene was switched on in mouse and human brains, supporting the theory that a mutation in the gene could play a role in psychiatric illnesses. They identified 10 different “single-letter” variations in the gene’s code that would lead to changes in the ABCA13 protein and which were not common in the controls.
Overall, these variations were more common in the people with psychiatric illnesses (schizophrenia, bipolar disorder, or depression) than in controls without the conditions. Analyses of the families of some of the individuals with these variations supported their association with the psychiatric illnesses. When the researchers looked at individual illnesses, variations were significantly more common in people with schizophrenia or bipolar disorder than in controls, but not in people with depression.
When the researchers looked at the genetic variations individually, they found that three particular variations were more common in people with bipolar disorder than in controls. Having a single-letter variation in the gene was more common in people with schizophrenia than controls. However, these differences were not statistically significant after the researchers took into account the multiple tests that they had carried out.
The researchers estimated that variations in the ABCA13 gene could account for 2.2% of the risk of schizophrenia in the general population, and 4.0% of the risk of bipolar disorder.
How did the researchers interpret the results?
The researchers concluded that they have identified variations in the ABCA13 gene that could contribute to the risk of schizophrenia, bipolar disorder and depression.
This research has identified a potential role of the ABCA13 gene in mental illness, particularly schizophrenia and bipolar disorder. However, the findings of this study will also need to be confirmed by other studies and in other populations.
Psychiatric illnesses are complex and varied, and their development is likely to be influenced by numerous genetic and environmental factors. While this type of study helps expand our knowledge of the biology of mental illness, it should not be expected to identify a single genetic cause for mental illness, as some of the news coverage may suggest. The variants identified in this research were estimated to potentially account for only about 2% of the risk of schizophrenia and 4% of the risk of bipolar disorder in the general population.
News coverage has also suggested that the discovery could lead to drugs that restore mental health in patients with psychiatric illness. However, the development of such drugs is likely to be a long way off, and it is unlikely that they would treat all types of mental illness.
Overall the findings of this study open up a new avenue for future research, but there is likely to be a lengthy delay before any potential drugs based on these findings could be developed.
Analysis by Bazian
Edited by NHS Website
Links to the science
Am J Hum Genet. November 25 2009