Groundbreaking study on migraine headaches opens path for future treatments

An international consortium of leading migraine scientists carried out the largest genome study of migraines to date. They identified 123 genetic regions of the genome that are connected to the risk of migraine, a news release notes.

The massive undertaking was a joint effort between research groups from Australia, Denmark, Estonia, Finland, Germany, Iceland, Netherlands, Norway, Sweden, UK and USA.

It helps researchers better understand the biological basis of migraine and its subtypes and could hasten the search for new treatment of the condition.

Migraine headaches affect one billion people globally, making one in six people susceptible to the condition.

With migraines affecting such a large portion of the world’s population, “it is important to learn about its biological background as a goal is to develop treatments for migraine,” Dr Matti Pirinen tells TRT World in an email. Pirinen is a group leader from the Institute for Molecular Medicine Finland, University of Helsinki, who led the study.

The study saw leading migraine research groups in Europe, Australia and the United States collaborate to pool genetic data from 873,341 individuals of European ancestry, 102,084 of whom suffered from migraines.

Published in the February 3, 2022 issue of Nature Genetics journal, the new findings also “uncovered more of the genetic architecture of migraine subtypes than was previously known,” the news release adds.

Migraines can be with or without aura. Migraine with aura (MA; also known as classic migraine) “is a recurring headache that strikes after or at the same time as sensory disturbances called aura,” says the Mayo Clinic. “These disturbances can include flashes of light, blind spots, and other vision changes or tingling in your hand or face.”

On the other hand, about 70-75% of migraine patients do not experience aura (MO).

“Both types [migraine with aura and migraine without aura] include pulsating and usually one-sided headaches that may be aggravated by physical activity and can be associated with symptoms such as a hypersensitivity to light and sound, nausea and vomiting,” Pirinen tells TRT World.

“The main difference is that migraine with aura starts with an aura phase that occurs before a headache. Aura appears as sensory disturbance. For example, a common aura symptom includes flashes of light, blind spots, or other disturbances of vision,” he explains.

Nobody knows for sure what causes migraine attacks, but experts believe that it is a neurovascular disorder with disease mechanisms both within the brain and the blood vessels of the head.

While past research has demonstrated genetic factors contribute significantly to migraine risk, doctors debate whether MA and MO share similar genetic background.

Researchers from the International Headache Genetics Consortium put together a large genetic dataset to carry out a genome-wide association study (GWAS), seeking insight into specific risk genes that manifest as MA or MO.

They found that migraine subtypes have both shared risk factors, the news release notes, and risk factors that appear specific to one subtype. Their analyses highlighted three risk variants that seemed to be specific for MA (in HMOX2, CACNA1A and MPPED2) and two for MO (near SPINK2 and near FECH)  as well as “nine that increase susceptibility for migraine regardless of subtype,” the authors write.

 “In addition to implicating tens of new regions of the genome for more targeted investigation, our study provides the first meaningful opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes,” says the first author of the study, Heidi Hautakangas from the Institute for Molecular Medicine Finland, University of Helsinki.

Moreover, the results reinforced the idea that a migraine is “truly a neurovascular disorder”, brought about by both neuronal and vascular genetic factors.

Due to the fact that migraine is “globally the second largest contributor to years lived with disability, there is clearly a large need for new treatments,” the researchers write.

A “particularly interesting” finding, the news release notes, was the “identification of genomic risk regions containing genes that encode targets for recently developed migraine-specific therapeutics.”

“The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F),” the researchers note in the study.

“These two new associations near genes that are already targeted by effective migraine drugs suggest that there could be other potential drug targets among the new genomic regions,” Pirinen comments in the news release, “provid[ing] a clear rationale for future genetic studies with even larger sample sizes”.