{"id":50,"date":"2018-08-14T13:37:06","date_gmt":"2018-08-14T13:37:06","guid":{"rendered":"https:\/\/website.prod.unilu.spikeseed.cloud\/lcsb-fr\/news\/identification-of-a-risk-factor-in-genetic-generalised-epilepsies\/"},"modified":"2018-08-14T13:37:06","modified_gmt":"2018-08-14T13:37:06","slug":"identification-of-a-risk-factor-in-genetic-generalised-epilepsies","status":"publish","type":"news","link":"https:\/\/www.uni.lu\/lcsb-fr\/news\/identification-of-a-risk-factor-in-genetic-generalised-epilepsies\/","title":{"rendered":"Identification of a risk factor in genetic generalised epilepsies"},"content":{"rendered":"<section class=\"wp-block-unilux-blocks-free-section section\"><div class=\"container xl:max-w-screen-xl\"><p>Five researchers of the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg participated in an international collaboration involving several European consortia (Epicure, EuroEPINOMICS CoGIE and EPIPGX) together with labs from Australia and Canada working on epilepsy.<\/p><p>This project, that aimed to investigate the genetic burden in genetic generalised epilepsy (GGE) and has spanned several years, has successfully ended with a <a href=\"https:\/\/www.thelancet.com\/journals\/laneur\/article\/PIIS1474-4422(18)30215-1\/fulltext\" target=\"_blank\" title=\"\" rel=\"noopener\">recent publication in The Lancet Neurology<\/a>. \u201cThis is the largest genetic study with researchers of the LCSB in the lead so far\u201d points out Dr Patrick May, first author and senior researcher in the Bioinformatics Core who co-lead the analysis at the LCSB with Dr Roland Krause. It provided strong evidence that variation in genes encoding GABAA receptors &#8211; GABA being the major inhibitory neurotransmitter in the central nervous system &#8211; constitute a significant risk factor for GGE.<\/p>\n<h2 class=\"has-text-align-left wp-block-unilux-blocks-heading\"        id=\"a-complex-genetic-architecture\"\n    >\nA complex genetic architecture<\/h2>\n<p>Genetic generalised epilepsy is the most common type of inherited epilepsy but the genetic background of this group of diseases, is still poorly understood. It probably involves a complex inheritance meaning that many common and rare genetic factors play a role in the development of the disease. In this study, the researchers set off to investigate this intricate architecture by comparing the genetic information of large groups \u2013 called cohorts \u2013 of patients and controls (people from the common population who did not develop the disease in their early life). They looked for variations, first in the whole coding part of the genome, and then in a more targeted way by focusing on specific gene sets linked to the disease phenotype.<\/p>\n<h2 class=\"has-text-align-left wp-block-unilux-blocks-heading\"        id=\"the-central-role-of-gabaergic-mechanisms\"\n    >\nThe central role of GABAergic mechanisms<\/h2>\n<p>The results showed an increase in rare variants in the genes coding for the GABAA receptors, in three independent cohorts which together comprised more than 1000 patients affected by generalised epilepsy. This is \u2013 along with another study \u2013 the first evidence of a significant genetic burden in individuals with GGE and it is also the first time that the impact of a specific pathway is acknowledged. In addition, functional experiments were performed for some of the variants identified. They showed significant loss-of-function effects for four variants in two genes not previously associated with this group of diseases, suggesting an important contribution to the GGE phenotype.<\/p><p>These results reiterate the central role of GABAergic mechanisms in generalised epilepsies. They also highlight the interest of the methodology implemented in this study. \u201cThe discovery was only possible by joining efforts and combining different cohorts, allowing to increase statistical power,\u201d explains Patrick May. \u201cThe hypothesis-driven approach that allowed to focus on specific gene sets was also particularly successful.\u201d<\/p>\n<h2 class=\"has-text-align-left wp-block-unilux-blocks-heading\"        id=\"worldwide-study-to-follow\"\n    >\nWorldwide study to follow<\/h2>\n<p>The next step is called <a href=\"http:\/\/epi-25.org\/epi25-members\/\" target=\"_blank\" title=\"\" rel=\"noopener\">Epi25<\/a>: a multi-consortia study including American and Australian cohorts as well. In that framework, the same analyses will be performed on a worldwide data set including 25000 cases and 25000 controls. The sequencing has already started in the US. LCSB researchers Dr Patrick May and Dr Roland Krause will be part of the genetic analysis team and working on establishing the LCSB as an international data hub for genetic sequencing analysis in epilepsy.<\/p><p>&#8211; &#8211; &#8211;<\/p><p>Patrick May, Simon Girard, Merle Harrer, Dheeraj R Bobbili, Epicure Consortium, EuroEPINOMICS CoGIE Consortium, EpiPGX Consortium, Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study, <i>The Lancet Neurology<\/i>, August 2018, DOI: <a href=\"https:\/\/doi.org\/10.1016\/S1474-4422(18)30215-1\" target=\"_blank\" title=\"\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/S1474-4422(18)30215-1<\/a><\/p><p>This publication is available on <a href=\"http:\/\/hdl.handle.net\/10993\/36163\" target=\"_blank\" title=\"\" rel=\"noopener\">ORBilu<\/a>.<\/p><p>Funding: EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).<\/p><\/div><\/section>","protected":false},"excerpt":{"rendered":"<p>Five researchers of the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg participated in an international collaboration involving several European consortia (Epicure, EuroEPINOMICS CoGIE and EPIPGX) together with labs from Australia and Canada working on epilepsy.<\/p>\n","protected":false},"author":0,"featured_media":51,"template":"","format":"standard","meta":{"featured_image_focal_point":[],"show_featured_caption":false,"ulux_newsletter_groups":"","uluxPostTitle":"","uluxPrePostTitle":"","_trash_the_other_posts":false,"_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_tribe_ticket_capacity":"0","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false},"news-category":[],"news-topic":[18],"organisation":[],"authorship":[],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v22.3 (Yoast SEO v22.3) - 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