The genetics of bipolar disorder
Dr. John Vincent's research is helping to find the genes linked to this illness
In some cases, the connection between a genetic mutation and medical condition is clear. In cystic fibrosis, for instance, if person has mutations on a specific gene, the illness will occur. Knowing w
hich gene helps to develop new types of targeted treatments.
For mental illnesses, the situation is far more complex. Dozens of genes can influence a person’s risk for a particular mental health condition, which may or may not develop. But the goal in identifying these genes has the same purpose – to lead to improved, biologically based treatments.
In a new study published in BMC Medical Genetics
, CAMH Senior Scientist Dr. John Vincent
added to the growing body of knowledge on the genetics of bipolar disorder. This work confirmed the link between several known genes and bipolar disorder, and identified five new genes that were not previously connected.
“We’re all working toward establishing the ultimate set of genes associated with bipolar disorder, and then we can look at how they are involved in the functioning of neurons in the brain,” says Dr. Vincent, who heads the Molecular Neuropsychiatry and Development (MiND) Lab in the Campbell Family Mental Health Research Institute.
Bipolar disorder is marked by symptoms that alternate between phases of mania and depression, which can have a substantial impact on an individual’s life and daily functioning. It affects one to two per cent of the general population.
Identifying genetic markers
In this study, researchers scanned the DNA of more than 950 people with bipolar disorder to identify potential genetic markers, which were compared against the DNA of more than 950 people without the diagnosis. Half of the participants were from Canada and half were from a parallel study in the United Kingdom.
About 550,000 genetic variations were tested for each study participant. Each of these variations represents just one single alteration in the DNA building blocks that make up genes.
Through their analysis, Dr. Vincent and his team narrowed that number down from half a million to 68 genetic variations that appeared to be relevant. Their results were checked against the DNA of another group of 229 families with bipolar disorder.
They confirmed that a number of genes previously reported as associated with bipolar disorder, such as SYNE1 and CSMD1, were indeed highly likely to be connected to the condition. They also identified associations with five new genes, previously unconnected with bipolar disorder, all of which coded for proteins involved in brain-related functions such as signaling among cells.
Part of a global effort
Even though more than 2,000 people provided DNA samples, this type of research—known as a genome-wide association study—requires even larger numbers.
“We need to pool results with other studies to confirm there is a true association, and this requires many tens of thousands of people,” says Dr. Vincent. As a result, researchers around the world have been forming genetics consortia to combine their study results and collectively provide information on tens of thousands of people.
Once the knowledge of these biological targets are applied to treatment research, the outcome should ultimately benefit those with bipolar disorder, the same way that genetics research has contributed to making cystic fibrosis, a once-fatal disease, one in which people can live well into adulthood.
This study was supported by funding from the Canadian Institutes of Health Research and GlaxoSmithKline.