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World-first research uncovers intricate relationship between migraine, genetics, and brain size

More effective treatments for people who suffer from debilitating migraine headaches are a step closer thanks to world-first genetic research into the causes of the painful disorder.

Around one in four Australians are affected by migraine experiencing symptoms such as severe and prolonged headaches, nausea and vomiting, sensitivity to light and sound, and brain fog. Symptoms can last anywhere from a few hours to weeks and even months. Women are twice as likely to be affected.

Aside from the distressing impact on patients, migraine costs the Australian economy more than $35 billion every year, but there are still many unknowns about the biological causes of the complex condition with around half of all patients failing to respond to treatment.

A study led by QIMR Berghofer researcher Dr Brittany Mitchell, published in the journal Brain, has shown for the first time the genetic links between brain size and migraine risk.

“Our research found that a smaller brain size and smaller structures within the brain, such as the hippocampus and the amygdala, cause an increased risk of migraine, and that this might be due to shared biological pathways that affect neuronal signalling or the regulation of blood flow,” Dr Mitchell said.

“Migraine is a difficult disorder to treat so it’s very exciting that our research has delivered a better understanding of the biology of migraine which we hope will lead to more effective treatments.

“I know personally how debilitating migraines are because I suffer from them myself. Any step towards bringing relief to patients is always very exciting and positive.”

The research was made possible thanks to genetic data resulting from hundreds of thousands of participants from two multinational research collaborations – the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium and the International Headache Genetics Consortium (IHGC).

Co-author of the study, Professor Dale Nyholt from the QUT Centre for Genomics and Personalised Health is a world authority on the genetics of migraine and a leader of the IHGC.

He said identifying these new findings about the causal genetic links of migraine leads to new avenues for research.

“This latest research shows how vital research collaboration combined with the wealth of genetic data and analysis from IHGC and ENIGMA can increase understanding about the complex genetics causes of migraine with the ultimate goal of providing better treatments for patients and one day even being able to prevent this disorder,” Professor Nyholt said.

QIMR Berghofer genetic epidemiologist and study co-author, Dr Miguel Rentería, said the next step would be to further investigate the uncovered genes that are shared between brain structure and migraine risk and to also investigate if these genes are responsible for the differences in migraine risk between women and men.

“For the first time we can see that some of the genes that influence brain size can also increase migraine risk, and that this is in turn likely due to vascular regulation. We now want to study these shared genetic pathways to work out whether increasing blood flow, for example, could reduce migraine risk thereby opening up new possibilities for treatments,” Dr Rentería said.

The study has been published in the journal Brain and can be accessed via this link https://doi.org/10.1093/brain/awac105