Thursday September 2 2010
Migraine is a complex condition with a number of causes
Scientists have discovered genes that may be behind migraines, “opening the door to a cure”, reported the Daily Mirror. The newspaper said that these genes normally control the levels of a brain chemical called glutamate, but a variant form of the gene may lead to a build-up of glutamate within the nerve cells. According to the paper, halting this build-up could help stop migraines.
The study behind this story scanned the DNA of several thousand people with and without a history of migraine. It compared their genetics and identified a particular gene variant that was more common in migraine sufferers. The study adds to our understanding of the complex processes that lead to migraines and highlights that there may be genetic causes.
This is important research, but finding genes that are linked to a condition is very different from developing a safe treatment based on this knowledge. Overall, it is premature for newspapers to suggest that this research may soon produce a cure for migraines. Migraine is a complex condition in which the interaction between genes and the environment is likely to be important, meaning there may not be a single cause or cure.
Where did the story come from?
The study was carried out by researchers from the Wellcome Trust Genome Campus in Cambridge and from research groups across the world. The work was supported by several groups, including the Wellcome Trust, and was published in the peer-reviewed medical journal Nature Genetics.
Some newspapers optimistically announced that this study may lead to a cure for migraines, but a great deal of further research is needed before we know if this genetic discovery can improve the diagnosis or treatment of migraines.
What kind of research was this?
Migraine is an episodic headache disorder that is more common in women. The cause is thought to be related to changes in levels of particular chemicals in the brain and many potential triggers have been identified. These include dietary factors, physical triggers such as poor posture and tiredness, emotional triggers including stress, anxiety and depression, and environmental triggers. Some people also experience migraines after taking certain medications.
This was a genome-wide association (GWA) study which scanned people’s DNA to look for genetic factors that may be involved in migraines. GWA studies are commonly used to investigate whether particular genetic variants (such as mutations in DNA) are associated with certain conditions. The general approach is to assess the DNA sequences of a group of individuals with a condition and compare them to the DNA sequences in a group of unaffected individuals. In this study, researchers set out to identify genetic variants associated with the most common forms of migraine.
What did the research involve?
The researchers enrolled 3,279 people who suffered from migraines (cases) and 10,747 people who did not have the condition (controls). People were mainly recruited from headache clinics across Europe. Migraine was diagnosed by clinical experts through questionnaires and interviews.
As is common with this type of study, researchers then performed a “replication phase” to verify their initial findings in a separate, independent population. The replication phase examined separate samples of people from Denmark, Iceland, the Netherlands and Germany, plus a sample that combined all of these. In total, these replication tests examined a further 3,202 cases and 40,062 matched controls.
Migraine can sometimes be accompanied or preceded by visual distortions, called aura, which resemble bright rings of light. As well as being analysed as a single group, the participants who experienced migraines were further classified into subgroups based on their symptoms. These were a migraine with aura only group, migraine with and without aura group, and migraine without aura only group.
The researchers then assessed and discussed literature to identify the biological mechanisms that may be affected by the genetic variants identified.
What were the basic results?
The researchers identified one variant, called rs1835740, that was associated with migraine in both the initial and replication samples. People possessing the variant were about 1.5 to 1.8 times more likely to experience migraines than those without the variant. The researchers discussed what is known about the variant and its positioning within the DNA. They said that it is positioned between two genes that are involved in the body’s production of glutamate, a chemical in the brain that is involved in transmitting messages between nerve cells.
How did the researchers interpret the results?
The researchers concluded that their study has established a particular genetic variant (rs1835740) as a genetic risk factor for migraine. They say that, to their knowledge, this is the first time a study has done this.
This was a well-conducted and well-described genetic study that followed a recognised approach for studies in this field. There are some points to consider:
- One proposed cause of neurological disorders is a problem with ion channels (pores in the nerve cell walls that aid the transmission of nerve signals). The researchers say that in their study, they did not identify any associations between known ion channel genes and migraine.
- Possessing the rs1835740 genetic variant put people at an increased risk of migraine, but not all people with the variant experienced migraine. Conversely, some people without the variant experienced migraine, illustrating that other factors are also behind migraine.
- Despite speculation by newspapers, there is still more work to be done in this field and it is too soon to claim that a cure for migraine is on the way. While a particular genetic variant has been associated with migraine, it is unclear how this could lead to a cure as there is not yet any way to remove a variant from a person’s DNA. Drugs that block its action may one day be developed.
- The researchers note that the majority of their samples are from headache clinics and that their study needs replication in population-based samples.
The findings of this research increase our understanding of the biochemistry of neurological disorders, and this important study will pave the way for future research. These next research steps should also examine how genetics interact with the environment, as environmental triggers also play a part in the development of migraine.
The developing and testing of drugs can be a long and complicated process. If future studies result in improvements in the treatment of migraine, they are likely to be some way off.