LUMC researchers identify the first genetic risk factors for cluster headaches

20 July 2021• NEWSITEM

A team of international researchers, led by the LUMC, have identified the first genetic risk factors for cluster headaches. They found four genes that play a role in the development of this neurological disorder, which is characterized by attacks of excruciating headaches. This discovery is an important step in unravelling the exact cause of cluster headaches. The results are published in Annals of Neurology.

Cluster headache is a neurological disorder with recurrent excruciating headaches on one side of the head, typically around the eye. "Until now, we thought that genetic factors were less important in cluster headache than for instance in migraine, as we rarely see large families with multiple cluster headache patients," says professor and neurologist Gisela Terwindt.

Greater risk

However, genetic factors do appear to play a role in cluster headaches, Professor Arn van den Maagdenberg from the Department of Neurology and Human Genetics and colleagues found out. The researchers found four genetic variants that increase the risk of cluster headaches. To this end, they conducted a large genetic study, a so-called genome-wide association study.  

The Leiden researchers compared the genetic information of hundreds of thousands of genetic variants of more than 800 cluster headache patients from the Netherlands with that of 1000 controls. In this way, they were able to identify the genetic variants that increase the risk of cluster headaches. The Norwegian researchers were then able to confirm the variants found in a small group of almost 150 patients and about 1800 controls. In addition, another group of researchers found genetic risk factors in the same locations in the genome, strengthening the evidence for a genetic cause. 

"What makes our findings so interesting is that the difference between the patients and controls in both studies is greater than we usually see for other complex diseases such as type 2 diabetes and cardiovascular disease," said Aster Harder, researcher at the Department of Neurology and Human Genetics.

Strong evidence

"The discovery of four risk factors for cluster headache, in these admittedly small studies, provides strong evidence that the disease has a genetic basis," says Van den Maagdenberg. "This study is an important step in unravelling the biological mechanisms that cause cluster headaches. This will hopefully allow us to offer better treatments to these patients in the future," adds associate professor Raymond Noordam.  

Read the full article in Annals of Neurology, or visit the website of the LUMC for more information about headache studies.  

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