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Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments

Date:
August 31, 2023
Source:
RCSI
Summary:
The largest genetic study of its kind has discovered specific changes in our DNA that increase the risk of developing epilepsy and may inform the development of new treatments.
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The largest genetic study of its kind, coordinated by the International League Against Epilepsy, including scientists from FutureNeuro at RCSI University of Medicine and Health Sciences, has discovered specific changes in our DNA that increase the risk of developing epilepsy.

The research, published today in Nature Genetics, greatly advances our knowledge of why epilepsy develops and may inform the development of new treatments for the condition.

Epilepsy, a common brain disorder of which there are many different types, is known to have genetic component and to sometimes run in families. Here, researchers compared the DNA from diverse groups of almost 30,000 people with epilepsy to the DNA of 52,500 people without epilepsy. The differences highlighted areas of our DNA that might be involved in the development of epilepsy.

The researchers identified 26 distinct areas in our DNA that appear to be involved in epilepsy. This included 19 which are specific to a particular form of epilepsy called 'genetic generalized epilepsy' (GGE). They were also able to point to 29 genes that are probably contributing to epilepsy within these DNA regions.

The scientists found that the genetic picture was quite different when comparing distinct types of epilepsy, in particular, when 'focal' and 'generalized' epilepsies were compared. The results also suggested that proteins that carry electrical impulse across the gaps between neurons in our brain make up some of the risk for generalized forms of epilepsy.

"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 Professor Gianpiero Cavalleri, Professor of Human Genetics at RCSI School of Pharmacy and Biomolecular Science and Deputy Director of the SFI FutureNeuro Research Centre.

"The discoveries we report on here could only be achieved through international collaboration, on a global scale. We are proud of how the global community of scientists working to better understand the genetics of the epilepsies have pooled resources and collaborated effectively, for the benefit of people impacted the condition" commented Professor Cavalleri.

The researchers also showed that many of the current medications for epilepsy work by targeting the same epilepsy risk genes that were highlighted in this study. However, based on their data, the researchers were able to propose some potentially effective alternative drugs. These will need to be clinically tested for use in epilepsy as they are normally used for other conditions, but they are known to target some of the other epilepsy risk genes uncovered.

"This identification of epilepsy associated genetic changes will allow us to improve diagnosis and classification of different epilepsy subtypes. This in turn, will guide clinicians in selecting the most beneficial treatment strategies, minimising seizures" said Professor Colin Doherty, Consultant Neurologist, St James's Hospital, Co-author and Clinical Investigator at the SFI FutureNeuro Centre.

Over 150 researchers, based across Europe, Australia, Asia, South America and North America, carried out the research. They worked together as part of the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies. The ILAE Consortium was formed by researchers in 2010, recognising that the complexity of genetic and environmental factors underlying epilepsy would require research across massive datasets, and therefore unprecedented collaboration on an international scale.

"Undertaking such a comprehensive study is a remarkable achievement that RCSI and Futureneuro are proud to have played a leading role in. The challenge now is to translate the findings of this research to improve the lives of people with epilepsy" concluded Professor Cavalleri.

"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" said Professor Samuel Berkovic, University of Melbourne.

"This is a major milestone for the ILAE Consortium on Complex Epilepsies, demonstrating what can be achieved when scientists openly collaborate and share data from across the world. The outputs are wide-reaching and applicable to epilepsy patients globally." said Professor Helen Cross, President of the International League Against Epilepsy.

Science Foundation Ireland (SFI) supported the work through their funding of the Futureneuro Research Centre.


Story Source:

Materials provided by RCSI. Note: Content may be edited for style and length.


Journal Reference:

  1. Remi Stevelink, Ciarán Campbell, Siwei Chen, Bassel Abou-Khalil, Oluyomi M. Adesoji, Zaid Afawi, Elisabetta Amadori, Alison Anderson, Joseph Anderson, Danielle M. Andrade, Grazia Annesi, Pauls Auce, Andreja Avbersek, Melanie Bahlo, Mark D. Baker, Ganna Balagura, Simona Balestrini, Carmen Barba, Karen Barboza, Fabrice Bartolomei, Thomas Bast, Larry Baum, Tobias Baumgartner, Betül Baykan, Nerses Bebek, Albert J. Becker, Felicitas Becker, Caitlin A. Bennett, Bianca Berghuis, Samuel F. Berkovic, Ahmad Beydoun, Claudia Bianchini, Francesca Bisulli, Ilan Blatt, Dheeraj R. Bobbili, Ingo Borggraefe, Christian Bosselmann, Vera Braatz, Jonathan P. Bradfield, Knut Brockmann, Lawrence C. Brody, Russell J. Buono, Robyn M. Busch, Hande Caglayan, Ellen Campbell, Laura Canafoglia, Christina Canavati, Gregory D. Cascino, Barbara Castellotti, Claudia B. Catarino, Gianpiero L. Cavalleri, Felecia Cerrato, Francine Chassoux, Stacey S. Cherny, Ching-Lung Cheung, Krishna Chinthapalli, I-Jun Chou, Seo-Kyung Chung, Claire Churchhouse, Peggy O. Clark, Andrew J. Cole, Alastair Compston, Antonietta Coppola, Mahgenn Cosico, Patrick Cossette, John J. Craig, Caroline Cusick, Mark J. Daly, Lea K. Davis, Gerrit-Jan de Haan, Norman Delanty, Chantal Depondt, Philippe Derambure, Orrin Devinsky, Lidia Di Vito, Dennis J. Dlugos, Viola Doccini, Colin P. Doherty, Hany El-Naggar, Christian E. Elger, Colin A. Ellis, Johan G. Eriksson, Annika Faucon, Yen-Chen A. Feng, Lisa Ferguson, Thomas N. Ferraro, Lorenzo Ferri, Martha Feucht, Mark Fitzgerald, Beata Fonferko-Shadrach, Francesco Fortunato, Silvana Franceschetti, Andre Franke, Jacqueline A. French, Elena Freri, Monica Gagliardi, Antonio Gambardella, Eric B. Geller, Tania Giangregorio, Leif Gjerstad, Tracy Glauser, Ethan Goldberg, Alicia Goldman, Tiziana Granata, David A. Greenberg, Renzo Guerrini, Namrata Gupta, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Emadeldin Hassanin, Manu Hegde, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Henrike O. Heyne, Shinichi Hirose, Edouard Hirsch, Helle Hjalgrim, Daniel P. Howrigan, Donald Hucks, Po-Cheng Hung, Michele Iacomino, Lukas L. Imbach, Yushi Inoue, Atsushi Ishii, Jennifer Jamnadas-Khoda, Lara Jehi, Michael R. Johnson, Reetta Kälviäinen, Yoichiro Kamatani, Moien Kanaan, Masahiro Kanai, Anne-Mari Kantanen, Bülent Kara, Symon M. Kariuki, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Mitsuhiro Kato, Josua Kegele, Yeşim Kesim, Nathalie Khoueiry-Zgheib, Chontelle King, Heidi E. Kirsch, Karl M. Klein, Gerhard Kluger, Susanne Knake, Robert C. Knowlton, Bobby P. C. Koeleman, Amos D. Korczyn, Andreas Koupparis, Ioanna Kousiappa, Roland Krause, Martin Krenn, Heinz Krestel, Ilona Krey, Wolfram S. Kunz, Mitja I. Kurki, Gerhard Kurlemann, Ruben Kuzniecky, Patrick Kwan, Angelo Labate, Austin Lacey, Dennis Lal, Zied Landoulsi, Yu-Lung Lau, Stephen Lauxmann, Stephanie L. Leech, Anna-Elina Lehesjoki, Johannes R. Lemke, Holger Lerche, Gaetan Lesca, Costin Leu, Naomi Lewin, David Lewis-Smith, Gloria H.-Y. Li, Qingqin S. Li, Laura Licchetta, Kuang-Lin Lin, Dick Lindhout, Tarja Linnankivi, Iscia Lopes-Cendes, Daniel H. Lowenstein, Colin H. T. Lui, Francesca Madia, Sigurdur Magnusson, Anthony G. Marson, Patrick May, Christopher M. McGraw, Davide Mei, James L. Mills, Raffaella Minardi, Nasir Mirza, Rikke S. Møller, Anne M. Molloy, Martino Montomoli, Barbara Mostacci, Lorenzo Muccioli, Hiltrud Muhle, Karen Müller-Schlüter, Imad M. Najm, Wassim Nasreddine, Benjamin M. Neale, Bernd Neubauer, Charles R. J. C. Newton, Markus M. Nöthen, Michael Nothnagel, Peter Nürnberg, Terence J. O’Brien, Yukinori Okada, Elías Ólafsson, Karen L. Oliver, Çiğdem Özkara, Aarno Palotie, Faith Pangilinan, Savvas S. Papacostas, Elena Parrini, Carlos N. Pato, Michele T. Pato, Manuela Pendziwiat, Slavé Petrovski, William O. Pickrell, Rebecca Pinsky, Tommaso Pippucci, Annapurna Poduri, Federica Pondrelli, Rob H. W. Powell, Michael Privitera, Annika Rademacher, Rodney Radtke, Francesca Ragona, Sarah Rau, Mark I. Rees, Brigid M. Regan, Philipp S. Reif, Sylvain Rhelms, Antonella Riva, Felix Rosenow, Philippe Ryvlin, Anni Saarela, Lynette G. Sadleir, Josemir W. Sander, Thomas Sander, Marcello Scala, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Susanne Schubert-Bast, Andreas Schulze-Bonhage, Paolo Scudieri, Pak Sham, Beth R. Sheidley, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Michael C. Smith, Philip E. Smith, Anja C. M. Sonsma, Doug Speed, Michael R. Sperling, Hreinn Stefansson, Kári Stefansson, Bernhard J. Steinhoff, Ulrich Stephani, William C. Stewart, Carlotta Stipa, Pasquale Striano, Hans Stroink, Adam Strzelczyk, Rainer Surges, Toshimitsu Suzuki, K. Meng Tan, R. S. Taneja, George A. Tanteles, Erik Taubøll, Liu Lin Thio, G. Neil Thomas, Rhys H. Thomas, Oskari Timonen, Paolo Tinuper, Marian Todaro, Pınar Topaloğlu, Rossana Tozzi, Meng-Han Tsai, Birute Tumiene, Dilsad Turkdogan, Unnur Unnsteinsdóttir, Algirdas Utkus, Priya Vaidiswaran, Luc Valton, Andreas van Baalen, Annalisa Vetro, Eileen P. G. Vining, Frank Visscher, Sophie von Brauchitsch, Randi von Wrede, Ryan G. Wagner, Yvonne G. Weber, Sarah Weckhuysen, Judith Weisenberg, Michael Weller, Peter Widdess-Walsh, Markus Wolff, Stefan Wolking, David Wu, Kazuhiro Yamakawa, Wanling Yang, Zuhal Yapıcı, Emrah Yücesan, Sara Zagaglia, Felix Zahnert, Federico Zara, Wei Zhou, Fritz Zimprich, Gábor Zsurka, Quratulain Zulfiqar Ali. GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture. Nature Genetics, 2023; DOI: 10.1038/s41588-023-01485-w

Cite This Page:

RCSI. "Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments." ScienceDaily. ScienceDaily, 31 August 2023. <www.sciencedaily.com/releases/2023/08/230831142832.htm>.
RCSI. (2023, August 31). Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments. ScienceDaily. Retrieved October 31, 2024 from www.sciencedaily.com/releases/2023/08/230831142832.htm
RCSI. "Largest genetic study of epilepsy to date provides new insights on why epilepsy develops and potential treatments." ScienceDaily. www.sciencedaily.com/releases/2023/08/230831142832.htm (accessed October 31, 2024).

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