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A large genome-wide association study including more than 800,000 people has revealed previously unknown genetic variants linked to migraine and identified targets that could be used to develop new treatments for this common condition.

Although migraine, characterized by severe and recurring headaches, affects more than a billion people around the world, little is known about the contribution genetics makes to its pathology. Treatments have also advanced little in recent years.

To investigate the genetics behind migraine, Matti Pirinen, a group leader and senior researcher at the University of Helsinki in Finland, and colleagues carried out the largest known genomic study of migraine. As outlined in Nature Genetics, the study included 102,084 individuals with migraine and 771,257 controls, the participants came from various cohorts including the Norwegian Nord-Trøndelag Health Study, the UK Biobank, 23andMe and GeneRISK in Finland.

Migraine tends to split into two main subtypes, migraine with aura—visual or perceptual disturbances that often signal the onset of headache—and without aura. As part of the study, the researchers looked for genetic variants that could be linked to these two main types.

Overall, 123 areas of the genome linked to migraine were identified, 86 of which were previously unknown. These were linked to both neuronal and vascular factors, supporting previous research suggesting a neurovascular origin for migraine.

Regarding the two subtypes, three genetic variants in the genes HMOX2, CACNA1A and MPPED2 were linked with migraine with aura and two near the genes SPINK2 and FECH were associated with migraine without aura. Nine genetic variants were found that increase the risk for migraine regardless of type.

“In addition to implicating tens of new regions of the genome for more targeted investigation, our study provides the first meaningful opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes”, said the first author of the study, Heidi Hautakangas, from the Institute for Molecular Medicine Finland, University of Helsinki, in a press statement.

The team thinks the information they discovered from this study could help design new drugs for migraine. The study picked up two targets of relatively recent drugs for migraine, calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F).

“These two new associations near genes that are already targeted by effective migraine drugs suggest that there could be other potential drug targets among the new genomic regions, and provide a clear rationale for future genetic studies with even larger sample sizes,” said Pirinen.

The extra knowledge gathered in this study about genetic variants linked to subtypes of migraine could also help design better and more precise treatments for people affected by them. “Using genetic evidence when selecting new drug targets is estimated to double the success rate in clinical development,” write the authors.

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