New genetic links for migraine found

The Daily Mail today reported on “the genetic clue that may explain why women get more migraines”. The newspaper said that three genes had been linked to migraines and that they were “more likely to trigger migraines in women, helping to explain why they are three times more likely to suffer”.

The research was a large genetics study that looked at variations in DNA between people who experienced migraines and those who did not. Researchers compared the DNA of nearly 9,000 people who experienced migraines with 32,000 people who did not. They identified three regions of DNA that seemed to be associated with migraines. However, only two of these were specifically associated with migraines, rather than headaches in general.

Though one region was more strongly associated with migraines in women than men, the researchers say this association “would not explain the higher prevalence of migraine in women than men”.

Further research is needed to see how the genes that are close to these regions of DNA play a role in migraines. These study findings have no current implications for the prevention or treatment of migraines.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School and various European universities and research institutes. The study was funded by grants from the National Institute of Neurological Disorders and Stroke. The researchers used data from several cohort studies that had been funded by other sources. The study was published in the peer-reviewed scientific journal Nature Genetics.

The Daily Express covered the research accurately. The Daily Mail said that the research may explain why women are more likely to have migraines than men. However, though there was a stronger association between one of the regions of DNA and migraines in women, the researchers said that they didn’t know whether it was responsible for the difference in migraine risk between men and women.

What kind of research was this?

This genome wide association study investigated whether certain regions of DNA were associated with the risk of migraines.

This type of research investigates whether regions of DNA, called single nucleotide repeats or SNPs, are associated with medical conditions. SNPs are regions of DNA where one letter of the DNA sequence can vary between people at that location. The researchers compared the sequence in various SNPs between people with migraines (cases) and people who did not get migraines (controls).

Migraines are a common neurological disorder that can run in families, but the genetic influences are not fully understood. People’s experiences of migraines differ. For example, some people have visual disturbances before the migraine (aura) while others do not. The researchers made efforts to assess whether there were any genetic differences between people who experienced the different types of migraine.

What did the research involve?

The researchers compared the DNA sequence of 5,122 women who experienced migraines and 18,108 women who did not. The women were participating in the Women’s Genome Health Study.

The DNA of the women in these groups was examined to identify any SNP variations that were more common in the women who got migraines than the women who did not get migraines.

After they had found some SNPs that looked as if they could be associated with migraines, the researchers evaluated whether these SNPs were associated with migraines in two further cohorts. These were the Dutch Genetic Epidemiology of Migraine Study, which included 774 people with migraines and 942 people who did not get migraines, and the German Study of Health in Pomerania (SHIP), which included 306 people with migraines and 2,260 people who did not get migraines.

The researchers also looked at a third cohort, a previously reported clinic-based case-control sample from the International Headache Genetics Consortium (IHGC), which included 2,748 people with migraines and 10,747 people who did not get migraines. All the participants in the cohorts were of European ancestry.

What were the basic results?

In the first cohort, the researchers identified seven SNPs that looked as if they could be associated with migraines. Three of these SNPs also showed an association in the other three cohorts. These three SNPs were regions of DNA close to known genes. The first was near PRDM16, the second was near TRPM8 and the third was near LRP1.

The first cohort was a women-only cohort. The other cohorts were mixed. As migraines are more common in women than in men, the researchers carried out a separate analysis of these three associations in men and women of the groups to see if the association between the SNPs and migraines was also linked to gender. One of the SNPs (near TRPM8) was found to be strongly associated with migraines in women, but the association was not significant in men.

The researchers then looked at people’s experience of migraines: whether they had auras, were sensitive to light or sound, the location of their migraine pain, whether the pain had a pulsating quality, the typical duration of their migraine attack, whether their migraine was aggravated by physical activity and whether their migraine was accompanied by nausea or vomiting. The researchers found that none of these features had a particular association with the SNPs. Two out of the three SNPs were associated with migraines specifically, rather than non-migraine headaches.

How did the researchers interpret the results?

The researchers said that they have found three regions of DNA that are associated with migraines, two of which were specifically associated with migraine rather than non-migraine headaches.

One of the regions may be more strongly associated with migraines in women than men, but the researchers say that this does not “explain the higher prevalence of migraine in women than men”.

The genes TRPM8, LRP1 and PRDM16 were found to be close to the SNP regions of DNA that were associated with migraines. The researchers then discussed the known functions of these genes and whether it was biologically plausible that they were involved in migraines.

They suggest that the TRPM8 is responsible for a sensor that can detect cold sensation, including pain as a result of being exposed to cold. It has also been implicated as being involved in “neuropathic” pain (a pain that comes from signalling problems in the nerves). The researchers say that it is feasible that this gene could be involved in both migraines and neuropathic pain.

Meanwhile, LRP1 is thought to affect how neurons communicate between each other. The researchers say that this fits with recent medical approaches that target neuron signalling in migraines.

They say that the role of the third gene PRDM16 is not yet known.

Conclusion

This large genome wide association study found three regions of DNA that appear to be associated with migraines and identified genes that were close to these regions. Follow-up studies will look at these three genes to investigate how they could play a role in migraines. These regions of DNA were associated with migraines both with and without aura.

The research did not find that the genes themselves were “faulty” or “defective”, but that regions of DNA close to the genes had sequences that varied between people who had migraines and those who did not. It remains to be investigated what these DNA sequence variations do and the effect they have on nearby genes.

Although the Daily Mail reported that these findings may explain why women are more likely to have migraines than men, the researchers said that they didn’t know whether these associations were responsible.

This well-conducted and important research builds on our knowledge of the genetic influences of migraines. However, further understanding of the three genes and whether they play a role in migraines is needed before it is possible to say whether they could be used in treatments.