Tons of genetic variants underlying bipolar disorder have come to light
Danish researchers have helped identify 33 genetic variants that appear to play a role in bipolar disorder.
Danish researchers have helped identify 33 genetic variants that appear to play a role in bipolar disorder. To reach this stage, researchers had to trawl through the DNA profiles of 413,000 individuals.
Several scientific working groups are presently seeking to map the genetic architecture underlying hereditary mental illnesses such as schizophrenia, depression, and bipolar disorder.
This knowledge is much needed if the research is eventually to produce novel and more effective treatments for these diseases, which not only cause patients and their relatives great suffering but also place a huge financial burden on society.
However, it is a demanding job to map the genetic risk factors that, combined with environmental conditions, trigger mental illness, and it can only be achieved if large numbers of highly specialised researchers join forces.
The question is logical, but the answer is still – to some extent – blowing in the wind
The outcome of a collaboration between 230 leading researchers from universities in the USA, Germany, Denmark, Japan, Sweden, the Netherlands and the UK was recently published in the scientific journal Nature Genetics.
The research group studied genetic risk factors underlying bipolar disorder – for many years known as manic depression. And their work included studies of the DNA profiles of 413,000 individuals of European descent: 42,000 patients with bipolar disorder and 371,000 people who do not suffer from this mental illness. By comparing the results of these two groups, the researchers were able to identify 33 genetic variants that appear to play a role in bipolar disorder.
One of the Danish participants in the study, Associate Professor Thomas Damm Als from the Department of Biomedicine at Aarhus University, explains that this more than doubles the number of mapped genetic variants – or genetic risk factors – underlying bipolar disorder:
‘We conducted three studies under the auspices of the international collaboration to map genetic risk factors underlying bipolar disorder. By the time we began work on the third, which has now been published in Nature Genetics, we had already identified 31 variants – so, it must be said that we’ve significantly enhanced understanding of the genetic architecture of this disorder.’
The 413,000 DNA profiles included in the study originate from 57 European health databases, and almost 7,000 of these come from iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research.
Understanding the disease and medication
But what are the researchers actually investigating when they seek to map genetic variants underlying a mental illness?
‘In general, we’re looking for specific patterns in the presence of large fragments of DNA which have several variants. An entire “library” has now been built up of genetic variants which may be present at various loci in human DNA,’ says Thomas Damm Als.
When we examine the DNA of individuals with a specific disorder, and then compare the results with the DNA of people who are not affected by the disorder, this “library” helps us identify whether the incidence of certain genetic variants is particularly high in connection with the disease in question.
‘This was how we found the 33 variants,’ says Thomas Damm Als: ‘But to reach this stage, we had to look for variants at eight million loci in each of the 413,000 DNA samples. It was a huge study, and it was only possible because more than 200 researchers were involved.’
But what does the presence of these variants mean in terms of risk of developing bipolar disorder?
As Thomas Damm Als points out, the question is logical, but the answer is still – to some extent – blowing in the wind:
‘The genetic variants don’t explain why someone develops bipolar disorder. They contribute in a variety of ways, but environmental factors also have a role to play – and there is a similar “cocktail” of inherited traits and environmental influences behind other mental illnesses, such as schizophrenia and depression.’
The genetic variants linked to bipolar disorder identified by the large international research team can, in no small measure, be related to brain functions. Some of the variants are involved in genes expressed in the brain; others have an influence on neural signalling.
This knowledge deepens our understanding of bipolar disorder and can also give us ideas for developing new medical treatments for the disorder. On the other hand, Thomas Damm Als points out that the study was not able to explain bipolar disorder in more detail:
‘We know, today, that bipolar disorder is more heritable than, for instance, depression – but we still don’t understand how these genetic factors and the environment interact. And we haven’t yet identified all relevant genetic variants.’
Even more DNA analyses are needed to develop a better understanding of the disorder. A similar study to map depression, currently being conducted by a large international research team, has produced much the same evidence. It was a long and difficult process to identify genetic variants specific to depression. A picture did not begin to emerge until the researchers had analysed around 500,000 DNA profiles.
‘In the case of all mental illnesses, studies need to be of a certain size before there is any likelihood of finding genetic variants that can be termed as risk factors,’ says Thomas Damm Als.
Bipolar disorder is a heritable mental illness which typically presents during adolescence. Sufferers experience periods of mania or hypomania. These periods, which are characterised by extreme elation and very high levels of activity, are followed by periods of depression.
Manic and depressive symptoms can, in some cases, occur simultaneously, or patients may quickly alternate between the highs and lows.
It is estimated that one to two percent of the population will develop bipolar disorder in the course of their lives.
Psychoeducation is used to treat bipolar disorder; programmes help people understand the disease and teach them how to cope.
Medication and psychotherapy also play vital roles, and treatment is tailored to the needs of the individual.
If the disease is well-controlled, patients can live a good life with bipolar disorder.
(Source: The Danish Mental Health Fund)