Scientists have identified the first genetic risk factor linked to a common type of migraine after examining the genetic data of over 50,000 individuals. The investigators say that this breakthrough gives them new insights into migraine triggers, which will hopefully lead to novel therapies to prevent episodes of migraine.
The researchers identified a higher risk of developing migraine among patients with a particular DNA variant on Chromosome 8 between two genes - PGCP and MTDH/AEG.
The specific DNA variant appears to regulate glutamate levels, the scientists added. Glutamate is a neurotransmitter, which transport messages between nerve cells and the brain. The accumulated levels of glutamate in the synapses (nerve cell junctions) probably play a major role in starting migraine attacks.
A possible way of preventing migraine attacks might be to prevent the accumulation of glutamate at the synapse.
You can read about this study in the journal Nature Genetics.
Approximately 1 in every 6 females and 1 in every 12 males are affected by migraine. In the USA and EU migraine is estimated to be the most costly brain disorder in society. According to the World Health Organization (WHO), it is one of the top 20 diseases with years life with disability. A report in the USA puts the estimated costs of migraine on a par with diabetes.
This is the first time a genetic variant linked to a common form of migraine that has been identified, the authors write. There have been previous studies which describe genetic mutations which probably cause rare forms of the condition.
Dr Aarno Palotie, chair of the International Headache Genetics Consortium at the Wellcome Trust Sanger Institute, which spearheaded the study, said:
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.
Studies of this kind are possible only through large-scale international collaboration - bringing together the wealth of data with the right expertise and resources - so that we could pick out this genetic variant. This discovery opens new doors to understand common human diseases.
The scientists carried out a GWAS - genome-wide association study - to "zoom in on" genome variants that might be linked to migraine attacks.
The genomes of over 3,000 migraine-sufferers in Germany, The Netherlands and Finland were compared to the genomes of over 10,000 people who never had a migraine attack. Their aim was to identify differences which may explain one group's susceptibility to migraines. They also compared the genomes of another 3,000 migraine patients with over 40,000 people who never had a migraine attack.
They discovered that a DNA variation between the PGCP and MTDH/AEG-1 genes on chromosome 8 appeared to be linked to higher migraine risk.
The DNA variant seems to alter MTDH/AEG-1 activity inside the cells, which regulates the activity of the EAAT2 gene. The EAAT2 gene (a protein) is responsible for clearing glutamate from the synapses in the brain. Previous studies had linked EAAT2 with other neurological conditions/diseases, such as schizophrenia, some anxiety disorders, mood disorders, and epilepsy.
Professor Christian Kubisch, co-senior author, of the University of Ulm, Germany (previously at the University of Cologne, Germany where he conducted his research for this study), said:
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. 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.
Further studies are required to examine the DNA variant and its regulatory effect on the genes next to it, in order to understand the mechanism of occurrence of migraine attacks, the authors stress. More research is also needed to seek out additional contributing genetic factors, they add. They also suggest that broader population samples should be interrogated.
Dr Gisela Terwindt of Leiden University Medical Center, another senior author, said:
Although the patients in the study were all diagnosed with common migraine, they were largely recruited from specialist headache clinics. Because they are attending headache clinics they are likely to represent only the more extreme end of those who suffer common migraine. In the future, we should look at associations across the general population, including also people who are less severely affected.
"Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1"
Verneri Anttila, Hreinn Stefansson, Mikko Kallela, Unda Todt, Gisela M Terwindt, M Stella Calafato, Dale R Nyholt, Antigone S Dimas, Tobias Freilinger, Bertram Müller-Myhsok, Ville Artto, Michael Inouye, Kirsi Alakurtti, Mari A Kaunisto, Eija Hämäläinen, Boukje de Vries, Anine H Stam, Claudia M Weller, Axel Heinze, Katja Heinze-Kuhn, Ingrid Goebel, Guntram Borck, Hartmut Göbel, Stacy Steinberg, Christiane Wolf
Nature Genetics. Year published: (2010) DOI: 10.1038/ng.652
Published online 29 August 2010
Written by Christian Nordqvist