Unraveling the role of non-coding rare variants in epilepsy.

Autor: Girard A; Centre Intersectoriel en Santé Durable, University of Quebec in Chicoutimi, Saguenay, Canada., Moreau C; Centre Intersectoriel en Santé Durable, University of Quebec in Chicoutimi, Saguenay, Canada., Michaud JL; CHU Sainte-Justine, Montréal, Canada.; Department of Neurosciences and Department of Pediatrics, University of Montreal, Montréal, Canada., Minassian B; The Hospital for Sick Children, Department of Pediatrics, Toronto, Canada.; Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, Texas, United States of America., Cossette P; CHUM Research Center, Montréal, Canada.; Department of Neurosciences, University of Montreal, Montréal, Canada., Girard SL; Centre Intersectoriel en Santé Durable, University of Quebec in Chicoutimi, Saguenay, Canada.; CERVO Research Center, Laval University, Québec, Canada.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Sep 27; Vol. 18 (9), pp. e0291935. Date of Electronic Publication: 2023 Sep 27 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0291935
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Girard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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