Scientists take a step closer to unlocking the genetic causes of migraines
If you suffer from migraines, you’ll know just how debilitating they can be. They are among the world’s most common diseases, affecting around 14.7% of the world’s population and, until now, the underlying genetic causes have eluded scientists.
A study, published in the journal Neuron, throws new light on the reasons for migraines, painting a picture of how a person’s genes could increase their chances of suffering from the disease.
“For a long time, we have been wondering why common diseases (like migraine) aggregates in families,” said Aarno Palotie of the Institute for Molecular Medicine in Finland and the Broad Institute of MIT and Harvard.
Previous research has pointed to the potential for specific genes (CACNA1A, ATP1A2 and SCN1A) to cause a particularly severe form of migraine, called a hemiplegic migraine. One theory of how migraines are inherited hinges on the influence of a few, powerful genes such as these. In their study, Palotie and his colleagues set about finding whether this is indeed the case by investigating the medical history and genetic data of 1,589 families of known migraine sufferers in Finland, encompassing 8,319 individuals.
The researchers compared the presence of the three known, rare, hemiplegic migraine genes in the dataset with that of common genetic variants associated with migraines. To do this, they gathered data from an older genome-wide association study, which flags the locations of chromosomes that differ in people with specific diseases. These thousands of common variants, each contributing a tiny, individual effect, were then incorporated into the study of Finnish families.
“The actual surprise in this study was that in families with a lot of migraine cases, a significant part of the genetic risk is caused by common variants; the same variants that confer the disease risk in the general population,” Palotie told Alphr.
“It just seems that these families have an extra load of these variants that are common risk alleles in the population. Our previous thinking was too much geared on low frequency or rare high-impact variants, where one variants generates a high risk for the disease.”
Even for 45 families in the study that did suffer from the extreme hemiplegic migraine, only four of these cases were driven by the rare genes.
“The strength of the common variants in these families surprised us,” said Palotie.
The results suggest that migraines are caused, to a large degree, by polygenic inheritance; where a group of genes collectively influence a characteristic. What does this mean for how we think about migraines? Well, it shows the genetic causes are complex, and can rely on thousands of small variants, not just a few powerful genes. The researchers plan to build on this with further investigations, creating an even more comprehensive picture of the genes that contribute to the disease.
The hope is that, the more we understand the causes for inheriting migraines, the closer we get to developing new medicines for targeting them.
“This research provides additional understanding of the genetic background of migraines, which helps us to understand the basic disease mechanisms,” explained Palotie. “To understand the biological basis of a disease is the first step towards new therapies.”