In the largest-ever genetic study of migraines, a group of scientists led by researchers at Harvard and at the Broad Institute found dozens of new genetic variants associated with these sometimes debilitating headaches that are estimated to affect as many as a billion people worldwide.
Along with identifying 44 variants associated with migraines, the findings also point to vascular dysfunction as one of the biological underpinnings for the disease. Researchers have debated for years whether vascular or neuronal dysfunction could explain a propensity for migraines. This study provides the first genetic evidence pointing to vascular dysfunction as a potential cause.
“We provide evidence that migraine-associated genes are involved both in arterial and smooth muscle function,” the researchers wrote. “These results suggest that vascular dysfunction and possibly also other smooth muscle dysfunction likely play roles in migraine pathogenesis.”
Migraines often involve debilitating pain that can last many hours, or, in some cases, days. Beyond the pain, the symptoms can trigger nausea, vomiting, and for some who suffer from migraines with auras, distorted vision or seeing flashes of light. This subtype of migraine includes symptoms that often occur before a migraine starts, where those with the condition report having blind spots in their vision, or seeing bright lights or other patterns. Although the researchers looked, they were not able to detect any genetic associations that would differentiate the two types of migraines.
The 44 genetic variants they did identify are located in 38 genes or gene regions and many of those loci are involved in regulating vascular tissue and soft muscle tissue like that found inside of blood vessel walls. Of the genetic variants associated with migraines, 28 were identified for the first time.
These findings are consistent with research that shows that individuals who suffer from migraines are at a higher risk for stroke and cardiovascular disease. Interestingly, the researchers also found that the same genetic variant in the PHACTR1 gene that is associated with risks for a tear in arteries in the neck — a phenomena called Cervical Artery Dissection that is a common cause of strokes for people under 50 — is also associated with migraines.
The researchers of the study, published this week in the journal Nature Genetics, performed a meta-analysis that gathered 22 different genome-wide association studies and included data from more than 375,000 individuals from around the world.
About 173,000 of those individuals are 23andMe customers who consented to research. The 23andMe cohort was by far the largest used by the researchers. Much of the other data was collected together by the International Headache Genetics Consortium and included contributions from researchers in the UK, Iceland, Finland, Germany, the Netherlands, Australia and Estonia. This work also follows on a study done by the consortium.
“We simply can’t overstate the importance of international collaboration when studying genetics of complex, common diseases,” said Palotie who heads up the International Headache Genetics Consortium and works as a Research Director at the Institute for Molecular Medicine Finland, University of Helsinki, as well as serving as an associate member at the Broad Institute of MIT and Harvard.
The findings from this study could be a first step in developing new treatments for migraines, the researchers said.