A massive international study designed to unearth new knowledge around the causes of migraines has turned up some interesting new insights, with the authors effectively tripling the number of known genetic risk factors for the ailment. The findings also shed new light on what drives different types of migraines, and add weight to the idea that it is a neurovascular disorder.

Though they are incredibly common and affect more than a billion people around the world, scientists still don’t know exactly what causes migraines, a form of headache that can include severe throbbing and pain, and often visual disturbances known as auras. Research has shown that genetic factors can contribute to migraine risk, but questions remain over how they influence the occurrence either of a migraine with aura or a migraine without aura, the two main subtypes of migraine.

The study was carried out by research groups from Europe, Australia and the US and involved genetic data from more than 873,000 participants, with 102,000 of those suffering from migraines. The scientists conducted a genome-wide association study on these patients, on the hunt for genetic variants that were first of all common in those who had migraines, but could also differentiate the risk of one subtype over the other.

Pinpointing 123 regions of the genome that were connected to the risk of migraine, which tripled the amount known prior to the study, the scientists found that both subtypes shared certain risk factors, but some appeared relevant to one subtype only. More specifically, three risk variants were seemingly linked to migraine with aura, and two were linked to migraine without aura.

“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 University of Helsinki.

The scientists say the analysis further indicates that migraines are driven by a combination of neuronal and vascular genetic risk factors, in turn strengthening the idea that it is a neurovascular condition related to blood flow in the brain. Interestingly, two of the 123 newly identified genetic regions contain genes already targeted by new migraine drugs. One region, called CALCA/CALCB, which is implicated in migraine attacks, can be blocked by a recently developed inhibitor drug, while another, which covers the HTR1F gene, is also the target of cutting-edge migraine medications.

“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 Dr. Matti Pirinen from the University of Finland, who led the study.

The research was published in the journal Nature Genetics. 

Source: University of Helsinki