Large genetic analysis reveals new clues to the biological roots of migraine

In the largest study of migraines to date, researchers have identified a further five genetic regions that are linked to the onset of migraine. The findings open new doors to understanding the biological triggers that underlie migraine attacks.

Migraine is a debilitating disorder that affects around one in seven people. It was recognised as the seventh highest cause of disability in the world in the Global Burden of Disease Survey 2010, and it has been estimated to be the most costly neurological disorder.

Migraine is an extremely difficult disorder to study because no biological markers have yet been linked to episodes of migraine or the time between attacks. In the study, the international team identified 12 genetic regions associated with migraine susceptibility; five of them had not been reported before and seven confirmed associations that had been reported in previous studies.

Eight of the regions were found in or near genes known to play a part in controlling brain circuitries, and two of the regions were associated with genes that are responsible for maintaining healthy brain tissue. The regulation of these pathways may be important in susceptibility to migraines.

"This study has greatly advanced our biological insight about the cause of migraine," says Dr Aarno Palotie, from the Wellcome Trust Sanger Institute. "Migraine and epilepsy are particularly difficult neural conditions to study; between episodes the patient is basically healthy, so it's extremely difficult to uncover biochemical clues."

The team identified the genetic regions by comparing the results from 29 different genomic studies, including more than 100,000 samples from migraine patients and control samples. They found that some of the regions of susceptibility lay close to a network of genes that are sensitive to oxidative stress, a biochemical process that results in the dysfunction of cells.

The team expects many of the genes at genetic regions associated with migraine are interconnected and could potentially be disrupting the internal regulation of tissue and cells in the brain, resulting in some of the symptoms of migraine.

"We would not have made discoveries by studying smaller groups of individuals," says Dr Gisela Terwindt, coauthor from Leiden University Medical Centre. "This large-scale method of studying over 100,000 samples of healthy and affected people means we can tease out the genes that are important suspects and follow them up in the lab."

The team identified an additional 134 genetic regions that may be linked to migraine susceptibility; however, the statistical evidence for these is much weaker. Other studies have shown that statistically weaker culprits can play an equal part in the underlying biology of a disease or disorder, but whether these particular regions have a role in susceptibility to migraine remains to be proven.

The study was published online this week in 'Nature Genetics'.