Epilepsy affects over 3 million Americans of all ages. Almost 500 new cases of epilepsy are diagnosed every day in the United States alone. Yet the genetics of many of the epilepsies are still not fully understood. Because science is made greater through collaboration, more than 61 researchers on 3 continents have joined together to form the Epi4K Consortium. Together, we are working to understand the genes that underlie epilepsy and its related disorders.
We are combining our separate research databases and participant DNA collections and will analyze more than 4,000 genomes, utilizing the most modern genetic techniques. We are looking for new genes, or changes within genes, which will point toward neural pathways that we can target for the development of new treatments for patients with epilepsy. Additionally, we hope that by creating a greater understanding of the genetics of epilepsy, we will one day be able to tailor an individual’s epilepsy treatment to their individual genetic make-up.
Our work is organized into 3 cores and 5 projects:
The Epi4k Administrative Core oversees and coordinates the activities of all cores and scientific projects. The Phenotyping and Clinical Informatics Core assembles, organizes and validates the phenotypic information on all patients proposed for genomic analysis, and ensures that patients’ DNA samples are available to the Epi4K Sequencing, Biostatistics and Bioinformatics Core when needed. The Sequencing, Biostatistics and Bioinformatics Core will service all of the Epi4k discovery projects by generating the necessary sequence data and prioritizing all genetic variants for validation in follow up cohorts.
- Duke University
- University of California, San Francisco
- University of Washington
- University of Melbourne
- Columbia University
- Université de Montréal
- Children’s Hospital of Philadelphia
- New York University
- Boston Children’s
- Royal College of Surgeons in Ireland
- Cincinnati Children’s Hospital
- Imperial College
- University of Liverpool
In Project 1, 500 patients with Infantile Spasms and Lennox-Gastaut Syndrome, along with their parents, will be sequenced to identify genetic causes of these syndromes, with the main hypothesis being that many of these patients have de novo mutations. Project 1 will also examine up to 250 families with polymicrogyria or periventricular heterotopia. The Project 2 team will perform whole genome sequencing on families with idiopathic generalized epilepsy (IGE) or non-acquired focal epilepsy (NAFE): 1,000 pairs of first-degree relatives, and 300 families with 3 or more individuals. Project 3, which will be carried out in collaboration with the CENet project in Canada, will explore genetic variants that influence epilepsy prognosis and response to treatment. Project 4 is tasked with inventing new computational algorithms to search for copy number variants (CNVs) in the genome data generated by Epi4K. The new Project 5 is the functional modeling team, which is developing new models of brains with the mutations/genes discovered by the consortium. Using these brain models, we can understand how the genes affect actual brain behavior, which will lead to the development of new drugs and therapies for epilepsy patients.
The Epi4K Consortium is supported by 6 grants from the National Institutes of Health, through the National Institute for Neurological Disorders and Stroke:
- U01NS077274 Administrative Core
- U01NS077276 Phenotyping and Clinical Informatics Core
- U01NS077303 Sequencing, Biostatistics, and Bioinformatics Core
- U01NS077364 Epileptic Encephalopathies
- U01NS077367 Whole Genome Sequencing in Multiplex Families and Pairs
- U01NS077275 CNV Detection