Gene variants implicated in migraines discovered

Newly discovered genetic variants could provide a better understanding of migraines, as well as targets for the development of new types of treatments.

Migraine is a neurovascular pain disorder affecting around 20 percent of adults. An international research group based in Iceland set out to investigate the genetics underpinning the condition in order to better equip clinicians to improve diagnosis, and to information development of targeted therapeutics.

'What makes our study unique is that it includes large datasets from sequenced individuals enabling detection of rare variants protecting against migraine, potentially opening an avenue for the development of novel drug targets,' said Professor Kari Stefansson, CEO of deCODE Genetics and lead author of the paper published in Nature Genetics.

The paper described how they examined the genome sequences of 1.3 million people of whom 80,000 had experienced migraines. High precision, whole genome sequencing in cohorts from six different European populations (which included Iceland, Denmark, the UK, the USA, Norway and Finland) revealed 44 major variants implicated in migraine.

There are two main subtypes of migraine: migraine with aura (which is the classical subtype with visual disturbances preceding a migraine) and migraine without aura. When looking at the results, 13 of the variants were found to be linked only with migraine without aura, and four newly identified variants were discovered to be associated specifically with migraine with aura.

One gene that drew particular attention was PRRT2 (previously known to be associated with a severe movement disorder in children, paroxysmal dyskenesia). A frameshift mutation in PRRT2 was found to cause an increased risk of migraine with aura, and in epilepsy, but not migraine without aura. Not only could this provide insight into migraines but also into overlapping pathways in migraine with other brain disorders.

'Migraine is well known to run in families, but it has not been easy to identify a clear genetic basis for each subtype,' said migraine researcher Professor Debbie Hay from the University of Otago, New Zealand, who was not involved in the study.

The researchers hope that this deeper understanding into the underlying biology of migraines will shift the attention of scientists to new therapeutic avenues.