US Pharm. 2022;47(3):4.

An international consortium of leading migraine scientists identified more than 120 regions of the genome that are connected to risk of migraine. The groundbreaking study helps researchers better understand the biological basis of migraine and its subtypes and could speed up the search for new treatment of the condition, which affects over a billion individuals worldwide.

In the largest genome study of migraine yet, researchers have more than tripled the number of known genetic risk factors for migraine. Among the identified 123 genetic regions are two that contain target genes of recently developed migraine-specific drugs.

The study involved leading migraine research groups in Europe, Australia, and the United States working together to pool genetic data from more than 873,000 study participants, 102,000 of whom had migraine. The new findings, published in Nature Genetics, also uncovered more of the genetic architecture of migraine subtypes than previously known.

Migraine is believed to be a neurovascular disorder with disease mechanisms within both the brain and the blood vessels of the head. Previous research has shown that genetic factors contribute significantly to the migraine risk. However, it has long been debated whether the two main migraine types—migraine with and without aura—share similar genetic backgrounds.

To gain more insight into the specific risk genes, researchers from the International Headache Genetics Consortium assembled a large genetic dataset to conduct a genome-wide association study, looking for genetic variants that were more common in those who had migraine in general or one of the two main migraine types. The results demonstrated that migraine subtypes have both shared risk factors and risk factors that appear specific to one subtype. The analyses highlighted 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 brought about by both neuronal and vascular genetic factors, strengthening the view that migraine truly is a neurovascular disorder. Migraine is globally the second largest contributor to years lived with disability. Therefore, there is clearly a large need for new treatments.

A particularly interesting finding was the identification of genomic risk regions containing genes that encode targets for recently developed migraine-specific therapeutics. One of the newly identified regions contains genes (CALCA/CALCB) encoding calcitonin gene–related peptide, a molecule involved in migraine attacks and blocked by the recently introduced calcitonin gene–related peptide inhibitor migraine medications. Another risk region covers the HTR1F gene encoding serotonin 1F receptor, also a target for new migraine-specific medications.

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