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Gang of four

Genetic variants influence migraine risk

Munich, 06/11/2012

Headache strikes out of the blue, noise or bright light suddenly becomes intolerable, nausea and vomiting follow. More than 10% of us experience episodes of migraine like this. LMU researchers have now for the first time identified four genes linked to the commonest form of the disorder.

Together with their colleagues from the International Headache Genetics Consortium, the Munich researchers have mapped four genetic risk factors in migraine patients to chromosomes 1, 3, 6 and 9. The new markers are relatively common “polymorphisms”, found at sites in the genome where single subunits of the DNA often vary within populations. According to Professor Martin Dichgans, Dr. Tobias Freilinger and Dr. Rainer Malik of the Institute for Stroke and Dementia Research at Munich University Hospitals, these risk factors make their carriers more susceptible than non-carriers to migraine without aura. This is the most common form of the condition, accounting for two-thirds of cases, and is defined by the absence of neurological symptoms such as the disturbances of vision responsible for the typical “aura”.

Statistical associations

“We compared genetic data from nearly 5000 migraine patients and over 7,000 controls,” says Dichgans. The objective was to identify among the millions of polymorphisms those variants that are statistically overrepresented in the patient population.

“Our findings are a major step in the unravelling of the molecular pathways of migraine”, says Freilinger. “The identified variants seem to point to brain hyperexcitability and vascular dysfunction as important mechanisms”.

A different risk factor was previously identified in patients suffering from migraine with aura. In that study, the results implied that an excess of glutamate, a neurotransmitter, at synapses (contact sites between nerve cells) predisposed to the condition. Freilinger is confident that work on larger patient populations will pinpoint further risk factors. (Nature Genetics, 10.06. 2012) math



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