Migraine study finds more genes that cause condition
“Hopes of a migraine cure have been boosted by the discovery of genes linked to the crippling headaches,” reports the Daily Mail.
This report is based on a study pooling genetic data collected in 29 studies in over 100,000 people, almost a quarter of whom experienced migraines. The researchers identified twelve loci (locations) in the DNA where specific genetic variations were more common in the people who experience migraines.
They then identified various genes in these loci which could be contributing to migraine risk. Most of these genetic variations were found to be located in the brain, and many of them are known to be involved in nerve cell function.
Researchers will now need to look at the genes in these regions more closely to be sure they are influencing migraine risk. Each individual gene is likely to contribute a small amount to a person’s susceptibility, and more associated locations are likely to be discovered.
Further understanding of the causes and therefore the biological pathways underlying migraine may help to develop new drug treatments. So we will need to wait to see if these findings lead to new treatments.
Where did the story come from?
The study was carried out by a large number of researchers from the International Headache genetics consortium.
It pooled results from a range of studies with an assortment of funding sources.
The study was published in the peer-reviewed journal Nature Genetics.
The Daily Mail’s coverage of this story is accurate but its headline is a little over-optimistic. Understanding the genetics of a condition and therefore the biological pathways that are affected may help researchers develop new treatments in the longer term, though it is not yet clear that this will be the case.
The Daily Telegraph’s headline (‘Five new genetic causes of migraine identified’) was more accurate in that it made clear the researchers were looking at the causes of migraine and not researching new treatments.
What kind of research was this?
This was an analysis looking for genetic variations associated with migraine. Migraine is reported to affect about 14% of adults, and a person’s genetics are thought to be part of the reason why they may be susceptible.
Identifying genetic variations associated with migraines will help researchers identify which genes might contribute to susceptibility. Multiple genes may contribute to a person’s susceptibility to migraine with each having a small effect,
A special type of case control study called a genome wide association study (GWA) aims to identify the locations in the DNA (loci) where these genes lie.
Large GWA studies are needed to detect their contribution, because each of the genes may contribute only a small amount to a person’s risk. In the current study, the researchers pooled data from 29 GWA studies to give them a much larger study capable of detecting these small effects.
What did the research involve?
The researchers pooled data collected in 29 international GWA studies, including 23,285 people who have migraines (cases) and 95,425 people who do not (controls). Some of the people with migraine came from migraine clinics (5,175 people), and some were recruited from the community (18,110 people).
These GWA studies use thousands of single “letter” variations spread across the DNA, and identify whether people who have migraine have specific variations significantly more often than people who do not have the condition. This shows these variations may lie in or near to genes that may be contributing to migraine risk.
As well as looking at all of the participants pooled together, the researchers also looked at three groups of people separately:
- people with migraine with aura (an aura is a warning sign that suggests that a migraine is coming, this may include visual signs such as flashing lights, or muscle stiffness)
- people with migraine without aura
- people who were seen in migraine clinic, who would be likely to have more severe migraines
When the researchers identified which genetic variations were more common in people with migraine, they looked at which genes were nearby and could be causing the association.
They also looked at whether these genes were active in tissue from regions of the human brain related to migraine.
This would support the possibility that they could be contributing to causing a susceptibility to migraine.
What were the basic results?
The researchers identified single letter variations in 12 different locations in the DNA that were more common in people with migraine.
Three of these locations showed the strongest association in people from the migraine clinics, and two showed the strongest association in people with migraines without aura.
Seven of these locations had already been found to be associated with migraine in previous studies, but five had never previously been found to be associated with migraine.
Eight of the locations contained single letter variations associated with migraine that lay within genes. The other four locations contained variations that were not in genes, but lay near to genes that could be playing a role.
Eight of the genes were known to be involved in the function of nerve cells.
Eleven of these genes were found to be at least moderately active in regions of the human brain related to migraine. The researchers also identified five other genes in these locations that were active in the brain.
How did the researchers interpret the results?
The researchers concluded that they have identified 12 locations on the DNA significantly associated with migraine, including five locations not previously known as being associated with the condition. They say that the number of locations they have identified is still modest in terms of gaining a broad understanding of migraine susceptibility. Also, as yet only tentative theories about how the identified locations contribute to migraine risk can be made.
Conclusion
This large study has identified a number of locations in the DNA that are associated with migraine susceptibility, and genes that may be responsible for these associations.
The finding that most of these genes are active in the brain supports the possibility that they are contributing to migraine risk, but this will need to be confirmed with further research.
The researchers were somewhat surprised that they did not find any locations specifically associated with migraine with aura, as genetic factors are thought to play a greater role in this form of migraine than in migraine without aura.
They speculated that one reason for this could be that there is more variability in the genetic factors affecting migraine with aura than migraine without aura, which would make them more difficult to detect.
Overall, this type of research adds to our understanding of what may be contributing to migraine risk, and this may help to develop treatments for migraine.
However, it is worth bearing in mind that developing new drugs takes a long time, and unfortunately it is not guaranteed that these findings will result in a “cure” for migraine.
