[en] Objective
Genetic generalized epilepsies (GGEs) comprise the most common genetically determined epilepsy syndromes, following a complex mode of inheritance. Although many important common and rare genetic factors causing or contributing to these epilepsies have been identified in the past decades, many features of the genetic architecture are still insufficiently understood. This study integrates genome‐wide association study (GWAS) data from the International League Against Epilepsy Consortium on Complex Epilepsies with transcriptome‐wide association studies to identify genes whose genetically regulated expression levels are associated with epilepsy.
Methods
To achieve this, we used multiple computational approaches, including MAGMA, a tool for gene analysis of GWAS data, and its derivatives E‐MAGMA and H‐MAGMA, to improve gene mapping accuracy by utilizing tissue‐specific expression and chromatin interaction data. Furthermore, we developed ME‐MAGMA to incorporate methylation quantitative trait loci data, providing insights into epigenetic factors.
Results
We identified a total of 897 false discovery rate‐corrected (<.05) candidates. These include voltage‐gated calcium channels, voltage‐gated potassium channels, and other genes such as NPRL2, CACNB2, and KCNT1 associated with epilepsy pathogenesis that act as key players in neuronal communication and signaling in the brain.
Significance
In this study, we propose new candidate genes to expand the dataset of potential epilepsy‐causing genes. Further research on these genes may enhance our understanding of the complex regulatory mechanisms underlying GGE and other types of epilepsy, potentially revealing targets for therapeutic intervention.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Neurology Genetics & genetic processes
Author, co-author :
Mushunuri, Ashwini ; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany ; Clinic for Plastic, Aesthetic, and Hand Surgery, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany ; Department of Engineering Brandenburg University of Applied Sciences Brandenburg Germany
Adesoji, Oluyomi ; Cologne Center for Genomics University of Cologne Cologne Germany ; University Hospital Cologne, Medical Faculty University of Cologne Cologne Germany
Lerche, Holger ; Department of Epileptology Eberhard Karls University Tübingen Germany
Becker, Albert ; Institute for Cellular Neurosciences II Medical Faculty, University of Bonn Bonn Germany
Grimm, Daniela ; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany ; Clinic for Plastic, Aesthetic, and Hand Surgery, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany ; Department of Biomedicine Faculty of Health, Aarhus University Aarhus Denmark
Nothnagel, Michael ; Cologne Center for Genomics University of Cologne Cologne Germany ; University Hospital Cologne, Medical Faculty University of Cologne Cologne Germany
Schulz, Herbert ; Department of Microgravity and Translational Regenerative Medicine, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany ; Clinic for Plastic, Aesthetic, and Hand Surgery, Medical Faculty, University Hospital Magdeburg Otto von Guericke University Magdeburg Germany
External co-authors :
yes
Language :
English
Title :
Genetic risk factor identification for common epilepsies guided by integrative omics data analysis
FNR16394868 - MechEpi-2 - Epileptogenesis Of Genetic Epilepsies, 2021 (01/01/2022-31/12/2024) - Alexander Skupin
Name of the research project :
U-AGR-7124 - INTER/DFG/21/16394868/MechEPI2 - SKUPIN Alexander
Funders :
FNR - Fonds National de la Recherche DFG - German Research Foundation
Funding number :
16394868
Funding text :
This research was funded by the German Research Foundation and the Luxembourg Fond Nationale de Recherche as a part of the research unit FOR-2715 (grants SHU3585/1.1, NO755/6-1, NO755/13-1, Le1030/16-2, INTER/DFG/21/16394868 MechEPI2, BE 2078/5-1, BE 2078/10-2).
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