Genetic Underpinnings for Migraines Uncovered

A team of researchers, all members of the International Headache Genetic Consortium, has uncovered 28 newly identified independent genomic regions associated with migraine by combining data from 22 genome-wide association studies that also included new data from approximately 35,000 migraine sufferers.

The findings from this study were published recently in Nature Genetics in an article entitled “Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.” From the millions of genetic variants analyzed, 38 independent genomic regions were shown to be associated with migraine—with only ten of these regions having been implicated in migraine susceptibility previously.

“Our consortium is devoted to uncovering the genetic causes of migraine and during the past few years we have been able to identify many risk variants,” explained senior study author Aarno Palotie, M.D., Ph.D., professor and associate member at the Broad Institute and leader of the International Headache Genetics Consortium “Yet, in this latest, large-scale study, tens of new genetic risk factors were discovered. Because all of these variants modify the disease risk only slightly, the effect could only be seen when this large amount of samples became available. We simply can't overstate the importance of international collaboration when studying the genetics of complex, common diseases.”

Migraines can be an incapacitating neurological disorder that affects one in seven individuals worldwide, yet the molecular mechanisms driving this malady have remained elusive. Researchers used DNA samples from 375,000 European, American, and Australian participants—with almost 60,000 of them suffering from migraine.

Interestingly, when the researchers took a closer look at the genomic areas pinpointed in the study, they noticed that most of them overlap with known genes. As many as nine of the genes have been previously associated with some vascular disease, and four more are known to be involved in the regulation of vascular tone, supporting the importance of blood vessels in migraine attacks.

“These genetic findings are the first concrete step towards developing personalized, evidence-based treatments for this very complex disease,” noted study co-author John-Anker Zwart, M.D., Ph.D., a professor at Oslo University Hospital. “We doctors have known for a long time that migraine patients differ from each other, and the drugs that work for some patients are completely inefficient for others. In the future, we hope that this information can be utilized in dividing the patients into different genetic susceptibility groups for clinical drug trials, thus increasing the chances of identifying the best possible treatment for each subgroup.”

Co-author Benjamin Neale, Ph.D., assistant professor at the Broad Institute of MIT and Harvard added that “these interesting findings linking migraine with vascular dysfunction were generated using novel computational approaches that utilize and combine data from various international biological databases. Such datasets are invaluable in situations like this when tissue samples from patients are not readily available, underscoring the importance of data sharing.”

The teams of researchers hailed from a dozen different countries including groups from Australia, Denmark, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Spain, Sweden, the UK, and the USA.