A variant of a particular gene has been linked with a significantly higher risk for developing migraines, according to a new study. The results could shed light on what triggers the recurring, intense headaches and may lead to new migraine therapies.
Chronic migraines afflict more than 300 million people worldwide, including roughly 1 in 6 women and 1 in 12 men. Severe head pain is often accompanied by nausea and extreme sensitivity to light and sound, according to the Mayo Clinic.
To pinpoint any genetic anomalies linked with the disorder, an international team of researchers compared the genomes of more than 2,700 migraine sufferers from Finland, Germany, and the Netherlands with the genomes of more than 10,000 people without the condition.
The research revealed that 25 percent of people with migraines have a genetic variant that appears to reduce activity in a neighboring gene. This gene is known to regulate a protein called EAAT2, which affects a neurotransmitter called glutamate.
Neurotransmitters are chemicals that transport signals between brain cells. The EAAT2 protein normally clears away glutamate—the most abundant neurotransmitter in mammal brains—once it's performed its function.
The scientists confirmed the gene variant is linked to migraines by comparing another 3,200 or so migraine patients from Iceland, Denmark, the Netherlands, and Germany with roughly 40,000 apparently healthy people.
Although past research had uncovered mutations that gave rise to rare and extreme forms of migraine, this is the first time a genetic variant has been linked to the common form of the condition, researchers said.
Better Migraine Drugs to Come?
Previous research has linked problems with EAAT2 regulation to other brain disorders, including epilepsy, schizophrenia, and various mood and anxiety disorders.
The new findings suggest that a buildup of glutamate in the brain might help initiate migraines and that preventing such accumulations could help fight the disorder.
"Glutamate inhibitors do exist now—some are used for epileptic-seizure treatments and for neurodegenerative disorders like Alzheimer's," said study co-author Aarno Palotie, chair of the International Headache Genetics Consortium at the Wellcome Trust Sanger Institute in the U.K.
"But whether they will work with migraine is another question we'll want answered," Palotie said.
Among Europeans, the genetic variant is also in 19 percent of nonmigraine patients, which suggests it's just one factor in migraine susceptibility.
"We want to follow up to see if we can identify other migraine-susceptibility genes," Palotie said. "Do they fit in the same cascade of effects involving glutamate, or are there other pathways involved in migraine as well?"
The migraine-genetics research was published online August 29 by the journal Nature Genetics.