7 February 2022

Genetic researchers can now explain different types of migraine


The world's largest gene study on migraine describes, for the first time, the genetic differences between migraine with and without aura. The results look promising for developing new medicines, says the Danish co-author.

Woman holding her head
For women between 20 and 40 years old, migraine is the most costly disease of all

Biological knowledge about the differences between migraine types has been improved enormously. In the largest genetic study of migraine ever, international research teams have found 86 new areas of genome that can be coupled to migraine, and this is more than three-times the area we already knew about. The results have just been published in the prestigious journal Nature Genetics and they provide important new knowledge about the mechanisms that lead to migraine attacks.

For the first time ever, there is now a genetic explanation demonstrating that migraine is not just migraine, but there are different genetic reasons for different types of illness. The health service is well aware that patients either have migraine with sensory disturbances, also called aura, or without sensory disturbances (without aura). However, this study is the first time that researchers have been able to identify three gene areas linked specifically to migraine with aura, and two gene areas which related specifically to migraine without aureole. At the same time, the study confirms the significance of three genes, which are targeted by recently developed migraine medicine.

In the long term, the results of the study may turn out to be extremely important for, among others, the more than half-million Danes who live with disabling migraine attacks. Thomas Folkmann Hansen is the researcher heading Rigshospitalet's research team for genomic research and an associate professor at the Novo Nordic Foundation Centre for Protein Research at the University of Copenhagen. He is at the sharp end of the Danish contribution to the study, which builds on many years of genetic research into migraine by the Danish Headache Centre and at the Danish Blood Donor Study.

“After this study, we can now genetically categorise migraine in a manner which makes very good biological sense. It is also the first time that we can link specific risk genes for migraine with targeted treatments for migraine attack. This looks very promising for the development of new medicines, and perhaps even medicines that can prevent other migraine symptoms than the headache itself,” said Thomas Folkmann Hansen.

He explained that there is currently no medicine that targets migraine with aura, but that the study now provides the genetic targets necessary to help researchers to focus their hunt in the development of new treatments.

The results are based on data from more than 870,000 test subjects, of whom 102,000 had a migraine. The study was carried out by an international consortium for headache researchers, with research teams from Australia, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Sweden, the UK, the USA and Denmark.

The four biological categories of migraine

With their new knowledge, the researchers are paving the way for a biological subdivision of migraine into four categories. The two first categories are migraine with or without aura, as is already common knowledge at the clinic. The third category is also specific for migraine, but it has not yet been associated with specific clinical characteristics in patients. The fourth category is not specific for migraine, but it makes people sensitive to migraine in some way. The last two categories can probably explain migraine symptoms and a general vulnerability to headaches,” said Thomas Folkmann Hansen.

The results of the gene study should be considered in light of the research debate on migraine, which for many years has focussed on two theories: According to one theory, migraine comes from disturbed signals in the brain, while according to the second theory a migraine attack is due to blood-vessel issues. Migraine attack can occur in two different ways, and this fits in well with the genetic profile of the disease that researchers have now described. 

Patients with aura often experience a migraine attack as visual impairment followed by headache and general migraine symptoms such as hypersensitivity to light, sound and smell, nausea and vomiting. Scans of these patients’ brains during an attack reveal coinciding disturbances in the cerebral cortex, and this is consistent with the first theory. However, the majority of patients with migraine without aura experience the attacks as a pulsating headache simultaneously with general migraine symptoms. This fits in well with the second theory that the genes can help regulate contraction of the blood vessels. This contraction is precisely what modern migraine medicines target,” explained Thomas Folkmann Hansen.

Second highest number of sick days

Migraine is very common and it affects many people during their life. In Denmark, around 50,000 patients are so severely affected that they have at least eight migraine attacks on a month. So many women between 20 and 40 years old are affected that migraine that it is the most costly disease of all for this group. In its most recent report, the World Health Organisation (WHO), assessed that migraine is the disease causing the second highest number of sick days globally, and it has enormous economic consequences for society.

Thomas Folkmann Hansen’s team is continuing its research in the area, and they will use the new knowledge to define which patients benefit from acute treatment and which need preventive treatment.

Read the entire study: Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles


Thomas Folkmann Hansen, Associate Professor at the Novo Nordisk Foundation Center for Protein Research and Rigshospitalet,  thomas.folkmann.hansen@regionh.dk , tlf. 2282 5659