Migraines linked to rare genetic variants that could boost treatments

An analysis of 1.3 million people’s genomes has revealed dozens of variations associated with migraines, which could lead to more effective treatments for the condition.

It is thought that up to 20 per cent of adults around the world experience migraines, which are recurrent and often incapacitating headaches that are hard to treat. Some people have sensory symptoms, such as flashing lights or tingling in the body, before the onset of a headache, while others don’t. It isn’t known why these two types of migraine – known as with or without aura – exist.

“Migraine is well known to run in families, but it has not been easy to identify a clear genetic basis for each subtype,” says Debbie Hay at the University of Otago in New Zealand.

Now, Kári Stefánsson at deCODE genetics, a biopharmaceutical company in Iceland, and his colleagues have identified the genetic variations that seem to influence whether or not people develop migraines.

The researchers analysed the DNA of 1.3 million people from Iceland, Denmark, the UK, the US and Norway, of whom around 80,000 experienced migraines.

They found 44 gene variants associated with the condition, 12 of which have never been described before. Of these, the team found that a rare variant of the PRRT2 gene, which helps regulate signalling between neurons, correlates with a large risk of migraine with aura, and epilepsy.

On the other hand, rare variants that suppress the function of the genes SCN11A and KCNK5, which play a role in transporting sodium and potassium between cells, respectively, appear to protect against both types of migraine.

The findings could lead to new treatments that target the causes of migraine, such as drugs that can inhibit the production of the proteins coded by the SCN11A and KCNK5 genes.

“Discoveries like this should offer substantial hope for the population who suffer from migraine,” says Stefánsson. “Current treatments do not completely abolish the tendency to develop migraines, so there’s a lot of room for better treatments.”

“Even though there have been tremendous recent advances in migraine care, there is still a great deal to do in understanding the mechanisms of migraine and how we can tailor treatment for each patient,” says Hay.

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