Constellation, le dépôt institutionnel de l'Université du Québec à Chicoutimi

Résumé

The discovery of new variants has leveled off in recent years in epilepsy studies, despite the use of very large cohorts. Consequently, most of the heritability is still unexplained. Rare non-coding variants have been largely ignored in studies on epilepsy, although non-coding single nucleotide variants can have a significant impact on gene expression. We had access to whole genome sequencing (WGS) from 247 epilepsy patients and 377 controls. To assess the functional impact of non-coding variants, ExPecto, a deep learning algorithm was used to predict expression change in brain tissues. We compared the burden of rare non-coding deleterious variants between cases and controls. Rare non-coding highly deleterious variants were significantly enriched in Genetic Generalized Epilepsy (GGE), but not in Non-Acquired Focal Epilepsy (NAFE) or all epilepsy cases when compared with controls. In this study we showed that rare non-coding deleterious variants are associated with epilepsy, specifically with GGE. Larger WGS epilepsy cohort will be needed to investigate those effects at a greater resolution. Nevertheless, we demonstrated the importance of studying non-coding regions in epilepsy, a disease where new discoveries are scarce.