Brain and brain waves in epilepsy, illustration

The largest genetic study of epilepsy to date, involving more than 150 researchers on four continents, has identified more than two dozen genetic regions that play a role in epilepsy development. The new findings, published today in Nature Genetics, have significantly advanced knowledge of the genetic underpinnings of the disease and may unlock the potential for more precise treatments based on each patient’s molecular profile.

In this study, researchers compared the DNA from a diverse population of nearly 30,000 people with epilepsy to that of more than 52,000 people without it, to discover regions in DNA that may increase the risk of developing the diseases. From their analysis, the researchers identified 26 distinct areas in human DNA that appear to be involved in the development epilepsy including 19 that are specific to the form of the disease called genetic generalized epilepsy (GGE). In addition, the investigators identified 29 genes that implicated in contributing to epilepsy within these DNA regions.

Digging deeper the research indicated additional potential markers of the disease in the proteins that transmit electrical impulses in our synapses as also influential in epilepsy and found that the genetic signature between focal and generalized epilepsies were distinct.

“Gaining a better understanding of the genetic underpinnings of epilepsy is key to developing new therapeutic options and consequently a better quality of life for the over 50 million people globally living with epilepsy,” said study participant Gianpiero Cavalleri, professor of Human Genetics at RCSI School of Pharmacy and Biomolecular Science and deputy director of the SFI FutureNeuro Research Centre in Ireland. “The discoveries we report on here could only be achieved through international collaboration,  on a global scale.”

The international research effort was conducted under the auspices of the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies. ILAE was formed in 2010 with the recognition of the complexity of epilepsy and the need for international collaboration due to the large datasets that would be required for in-depth research.

Other findings of the study showed that many current medications for epilepsy achieve their efficacy by targeting the same risk genes that the study detailed. The data also showed that there may be other drugs currently approved for other indications that could potentially be used as alternative to current medications. They investigators note that these other drugs would need to be tested clinically, but said they are known to target genetic regions that were implicated in epilepsy in their new findings.

“This identification of epilepsy associated genetic changes will allow us to improve diagnosis and classification of different epilepsy subtypes,” noted co-author Colin Doherty, consultant neurologist, St James’s Hospital and clinical investigator at the SFI FutureNeuro Centre. “This in turn, will guide clinicians in selecting the most beneficial treatment strategies, minimizing seizures.

Added Samuel Berkovic, a professor at University of Melbourne, Australia: “With this study, we have bookmarked parts of our genome that should be the major focus of future epilepsy research. It will form the basis for further work looking at the molecular pathways involved in seizure generation, neuronal dysfunction, and altered brain activity.”

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