Headache: it's also a question of DNA! Largest migraine study identifies more than 120 linked genes

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Elia Tabuenca García
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Massive new research has identified migraine as a DNA-related neurovascular disorder.

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A new study has identified more than 120 regions of the genome that are linked to migraine risk. The groundbreaking review helps better understand the biological basis of migraine and its subtypes, and it could speed up the search for a new treatment for this condition, which affects over one billion people around the world.





In the largest migraine study ever, researchers more than tripled the number of known genetic risk factors for migraines. Among the 123 genetic regions identified, there are two that contain migraine-specific drug target genes.

Leading migraine research groups in Europe, Australia and the United States were involved and worked together to bring together the genetic data of more than 873.000 study participants, 102.000 of whom had migraines. The new findings also revealed more of the genetic architecture of migraine subtypes than was previously known.

A systematic review

What has been identified through this new study is that i neurovascular mechanisms underlie the pathophysiology of migraine. The latter is a very common brain disease, with over a billion patients worldwide. The exact cause is unknown, but it is believed to be a neurovascular disorder with pathological mechanisms both within the brain and blood vessels of the head.

Previous research has shown that genetic factors contribute significantly to migraine risk. However, it has long been debated whether the two main types of migraine, namely migraine with aura and migraine without aura, share a similar genetic background.

To gain more insight into specific risk genes, researchers from the International Headache Genetics Consortium assembled a large set of genetic data to conduct a genome-wide association study (GWAS), at search for more common genetic variants in those who had migraines in general, or one of the two main types of migraine.

The results demonstrated that migraine subtypes have both shared risk factors and risk factors that appear subtype specific. Analyzes revealed three risk variants that appear to be specific to migraine with aura, and two that appear to be specific to migraine without aura. Furthermore, the results supported the concept that migraine is caused by both neuronal and vascular genetic factors, reinforcing the idea that this condition is truly a neurovascular disorder.



New Migraine Therapies

As migraines are a very common disease globally, there is clearly a great need for new treatments. A particularly interesting discovery was theidentification of genomic risk regions, containing genes that encode targets for recently developed migraine-specific therapies. One of the newly identified regions contains genes (CALCA / CALCB) that encode the gene-related peptide of calcitonin, a molecule involved in migraine attacks and blocked by inhibitory drugs. 

Another risk region covers the HTR1F gene encoding the serotonin 1F receptor, which is also a target of new specific drugs. These two new associations suggest that there may be other potentials for migraines, and provide clear rationale for future genetic studies with even larger sample sizes.

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Photos: Nature

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