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Transcriptomic and genetic analyses reveal potential causal drivers for intractable partial epilepsy

Guelfi, S; Botia, JA; Thom, M; Ramasamy, A; Perona, M; Stanyer, L; Martinian, L; ... Matarin, M; + view all (2019) Transcriptomic and genetic analyses reveal potential causal drivers for intractable partial epilepsy. Brain , 142 (6) pp. 1616-1630. 10.1093/brain/awz074. Green open access

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Abstract

Mesial temporal lobe epilepsy with hippocampal sclerosis represents the most common epilepsy syndrome in adult patients with medically intractable partial epilepsy. Mesial temporal lobe epilepsy is usually regarded as a polygenic and complex disorder, still poorly understood but probably caused and perpetuated by dysregulation of numerous biological networks and cellular functions. The study of gene expression changes by single nucleotide polymorphisms in regulatory elements (expression quantitative trait loci, eQTLs) has been shown to be a powerful complementary approach to the detection and understanding of risk loci by genome-wide association studies. We performed a whole (gene and exon-level) transcriptome analysis on cortical tissue samples (Brodmann areas 20 and 21) from 86 patients with mesial temporal lobe epilepsy with hippocampal sclerosis and 75 neurologically healthy controls. Genome-wide genotyping data from the same individuals (patients and controls) were analysed and paired with the transcriptome data. We report potential epilepsy-risk eQTLs, some of which are specific to tissue from patients with mesial temporal lobe epilepsy with hippocampal sclerosis. We also found large transcriptional and splicing deregulation in mesial temporal lobe epilepsy with hippocampal sclerosis tissue as well as gene networks involving neuronal and glial mechanisms that provide new insights into the cause and maintenance of the seizures. These data (available via the 'Seizubraineac' web-tool resource, www.seizubraineac.org) will facilitate the identification of new therapeutic targets and biomarkers as well as genetic risk variants that could influence epilepsy and pharmacoresistance.

Type: Article
Title: Transcriptomic and genetic analyses reveal potential causal drivers for intractable partial epilepsy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awz074
Publisher version: https://doi.org/10.1093/brain/awz074
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: co-expression regulatory network, hippocampal sclerosis, human brain eQTLs, mesial temporal epilepsy, splicing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10071979
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