First genetic link to common migraine found

In a first of its kind study, scientists have traced genetic risk associated with migraine attacks, which might make it possible for the novel therapeutics to prevent migraine attacks.

Researchers looked at the genetic data of more than 50,000 people.

The team found that patients with a particular DNA variant on Chromosome 8 between two genes - PGCP and MTDH/AEG-1 - have a significantly greater risk for developing migraine.

The team also discovered a potential explanation for this link. It appears that the associated DNA variant regulates levels of glutamate - a chemical, known as a neurotransmitter, which transports messages between nerve cells in the brain.

The results suggest that an accumulation of glutamate in nerve cell junctions (synapses) in the brain may play a key role in the initiation of migraine attacks.

Prevention of the build up of glutamate at the synapse may provide a promising target for novel therapeutics to ease the burden of the disease.

"This is the first time we have been able to peer into the genomes of many thousands of people and find genetic clues to understand common migraine," said Aarno Palotie of Wellcome Trust Sanger Institute.

The researchers carried out what is known as a genome-wide association study (GWAS) to zoom in on genome variants that could increase susceptibility to migraine.

The team compared the genomes of more than 3,000 people from Finland, Germany and The Netherlands with migraine with the genomes of more than 10,000 non-migraineurs, recruited from pre-existing studies, to spot differences that might account for one group's increased susceptibility to migraine.

To confirm their link, the team compared the genomes of a second group of more than 3000 patients with more than 40,000 apparently healthy people.

The statistical analysis revealed that a DNA variation found between the PGCP and MTDH/AEG-1 genes on chromosome 8 appears to be associated with increased susceptibility to common migraine.

"Although we knew that the EAAT2 gene has a crucial role to play in neurological processes in human and potentially in the development of migraine, until now, no genetic link has been identified to suggest that glutamate accumulation in the brain could play a role in common migraine," said Christian Kubisch of University of Ulm.

"This research opens the door for new studies to look in depth at the biology of the disease and how this alteration in particular may exert its effect," he added.

The International Headache Genetics Consortium published the findings.