About the Collaborative
In 2014, collaborators from around the world created the Epi25 Collaborative to exome sequence as many as 25,000 patients with epilepsy. The collaborative has generated 6,242 exomes in 2016, an additional 7,561 exomes in 2017, and has 1,005 ready for sequencing in 2018. The goal is to determine the extent to which rare and common epilepsies share genetic underpinnings and whether genetic risk arises from de novo mutations or from genetic variants.
With approximately 14,000 samples in 2017, Epi25 will be the largest epilepsy exome analysis to date, well-poised to address many of the issues that have challenged previous research projects:
- Sample Size: Epi25 plans to sequence as many as 25,000 exomes over a five-year period. By virtue of the number of exomes produced, the project is very likely to yield important new insights into the heritability of a broad range of epilepsies. If successful, this work will open doors toward future initiatives such as global precision medicine / clinical trial initiatives.
- Technology: Epi25 is partnering with the Broad Institute to run all exomes on the same chip and the same sequencers over a short period of time. No cohort in epilepsy will have such a large number of epilepsy exomes from a single exome platform.
- Clinical Data: Epi25 is gathering high-level clinical data for all participants to certify the epilepsy syndrome and the clinical features of each participant. This clinical data will clarify the phenotypic spectrum associated with gene variants and facilitate clinical translation.
By developing clinical phenotypic datasets to pair with a massive number of epilepsy exomes, we expect to find evidence that accurate and detailed phenotypic data reduces genetic heterogeneity, allows for identification of a well-matched replication cohort, and clarifies the phenotypic spectrum associated with a gene. This approach will help us address fundamental questions about the importance of rare variants, common variants, or de novo changes as the basis for specific forms of epilepsy.
All exomes slotted in Epi25 have been funded by NHGRI RFA-HG-015-001: Centers for Common Disease Genomics (CCDG) via its partnership with the Broad Institute. The CCDG is working across four sequencing centers to identify the genes and variation causing both common and rare diseases and to create a paradigm for understanding the genetic architecture of other common diseases. The database of phenotypic data will be shared worldwide to address questions about epilepsy syndromes and the functional effects of epilepsy genes, and to form the basis of future trials to develop precision medicine for genetic epilepsies.