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Scientists are looking at 44 gene variants that may be linked to migraine headaches. Tatiana Maksimova/Getty Images
  • Each year, more than 1 billion people around the world have a migraine headache.
  • Researchers from deCODE Genetics say they have identified 44 rare genetic variants — including 12 that are novel — associated with either migraine with aura or without.
  • Scientists believe these findings may pave the way for the development of new migraine therapies.

Every year, more than 1 billion people worldwide have at least one migraine headache, making it one of the most common neurological conditions in the world.

There is currently no cure for migraine — medications and avoiding triggers are used to treat symptoms when they occur as well as try to decrease migraine frequency.

Now, a large international study conducted by researchers from deCODE Genetics in Iceland has discovered 44 rare genetic variants — including 12 that are novel — associated with migraine with aura as well as without it.

In the study recently published in the journal Nature Genetics, researchers say they believe these findings will provide avenues for the development of new migraine therapies.

According to Gyda Bjornsdottir, PhD, a research scientist at deCODE Genetics and lead author of this study, while most studies of the genetics of migraine have focused on migraine as a single disease, several genetic associations have been found in migraine that are informative.

“The last article on migraine genetics associated over 120 common genetic variants with migraine,” Bjornsdottir told Medical News Today. “These are in different genes with different roles encoding different proteins.”

“We now had the resources and the numbers of whole genome sequenced individuals to study rare variants in association with migraine and to focus on the migraine subtypes with and without aura,” she added. “There is evidence that these are perhaps different pathologies to some extent — different biologies behind these subtypes of migraine.”

Dr. Kari Stefansson, the chief executive officer and co-founder of deCODE Genetics, told Medical News Today the research findings provide new evidence that migraine with and without aura are two separate conditions.

“Patients with migraine present in two ways — they present as patients who have an aura and then people who just descend with the headache without any preceding events,” Stefansson said. “These are clinically very distinct things.”

“What Dr. Bjornsdottir has done with her work is to demonstrate to us that this difference is not just a difference in perception by patients, it is biologically based,” he added. “She has shown unequivocally that even though there is an overlap between the pathogenesis of these two forms of migraine, the two of them are clearly very distinct.”

For this study, Bjornsdottir and her team analyzed genetic data from more than 1.3 million study participants of genome-wide association studies, of which 80,000 had migraine.

Focusing on genetic sequence variants associated with both migraine with and without aura, researchers discovered associations with 44 rare variants, 12 of which are novel.

One such variant is the PRRT2 gene, which was associated with a large risk of migraine with aura as well as epilepsy.

“Both are neurological diseases to some extent,” Bjornsdottir said. “Both diseases come in attacks of paroxysmal diseases that come and go. Both can have the elements of the aura mentioned. We calculated the genetic correlation between these two diseases in our data. And we do find that there is some genetic correlation, but they are not highly correlated. Indeed, this variant seems to be quite unique in terms of its affecting both epilepsy and migraine with aura in this biology that we detected.”

Another rare variant researchers found is the KCNK5 gene, which protects against severe migraine and brain aneurysm.

“Migraine has neurological and vascular etiologies to it,” Bjornsdottir explained. “Here we have a variant that is in a potassium channel gene that is expressed both in neurons and in arteries. We may have here evidence of biology that is common to migraine, both in terms of the neurological and vascular aspects of it, but we also might have a variant that may lead to severe headaches as a prequel to brain aneurysms.”

Stefansson said the more we understand about migraine, the more likely we are to find new ways to treat it.

“And we believe that with this study, Dr. Bjornsdottir has made a very meaningful contribution to our understanding of migraine,” he said. “So I think that this inevitably is going to increase the probability of the discovery of a new treatment. And besides that, the genes that were discovered encode proteins that are fairly attractive as (therapeutic) targets.”

As for the next steps in this research, Stefansson said they will be taking a look at the differences between migraine in men and women.

“Dr. Bjornsdottir is going to do a sex-based analysis to look at what are the genes that cause migraine in men and what are the genes that cause migraine in women,” he explained. “And that is important because we need to understand the sex differences.”

“There are considerable sex differences in the prevalence of migraine all over the world,” Bjornsdottir added. “We are pretty sure that there are some biological explanations for this, but what they are, we don’t know yet. So that’s the logical next step to study.”

Medical News Today also spoke with Dr. Medhat Mikhael, a pain management specialist and medical director of the non-operative program at the Spine Health Center at MemorialCare Orange Coast Medical Center in California who was not involved in the study.

It’s really an amazing study because it seems they can detect some of the novel genetic variants that can detect patients who are at high risk of development of migraine, and link those variants to other possible serious illnesses,” he said. “Like in (the) case of migraine with aura, they have linked it some with brain diseases like seizure, and others that misdiagnosed as migraine and ended up with a brain aneurysm. This is… an amazing study because it can make a huge change in the field of prevention and treatment of migraine.”

Mikhael said that identifying these novel genetic variants can help doctors with earlier migraine diagnosis and prevention, as well as helping to prevent misdiagnosis of migraine with other serious neurological conditions.

As this study was conducted in a genetic lab in Iceland, Mikhael said he would like to see this research advanced to the point where it can be used to test people with migraine through easier and simpler testing.

“That the testing process can advance to where we can see this available in some accessible labs for patients covered by insurance,” he said. “So we can do not only early detection, early diagnosis, early prevention, and avoid misdiagnosis and avoid complications like a bleeding aneurysm or stroke for a patient that was misdiagnosed as a migraine. Or has a migraine with aura, but someone missed some of the underlying seizure and hemiplegia that can happen with this patient because it was detected early, prevented early, and treated early.”