Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals.
Publication/Presentation Date
8-1-2019
Abstract
Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA
Volume
105
Issue
2
First Page
267
Last Page
282
ISSN
1537-6605
Published In/Presented At
Epi25 Collaborative. Electronic address: s.berkovic@unimelb.edu.au, & Epi25 Collaborative (2019). Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals. American journal of human genetics, 105(2), 267–282. https://doi.org/10.1016/j.ajhg.2019.05.020
Disciplines
Medicine and Health Sciences
PubMedID
31327507
Department(s)
Department of Medicine
Document Type
Article