ArticleGenome biology2016
Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Pooled it
- Precision Medicine in Epilepsy: Diagnostic Yield by Next-Generation Sequencing and Genotype-Phenotype Findings in a Romanian Cohort.International journal of molecular sciences · 2026Article
- Protein-protein interaction network architecture of human polygenic traits reveals domain-spanning connectivity and evolutionary pressures.Genome biology · 2026Article
- A transient sex-biased transcriptional program shapes early postnatal L2/3 neuron development.Biology of sex differences · 2026Article
- Functional characterization of a human epilepsy-associated gene network reveals metabolic regulation as a critical factor underlying seizure susceptibilities.Disease models & mechanisms · 2026Article
- Integrating rare and common variation in epilepsy genetics: from genetic architecture to penetrance and clinical expressivity.Frontiers in genetics · 2026Review
- Temporal Dynamics of tsRNA Regulation Mark an Abrupt Transition After Epileptogenesis.Journal of neurochemistry · 2025Article
- Article
- Identifying Novel Drug Targets for Epilepsy Through a Brain Transcriptome-Wide Association Study and Protein-Wide Association Study with Chemical-Gene-Interaction Analysis.Molecular neurobiology · 2023Article
- Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress.Epilepsia · 2022Review
- A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.Neuropathology and applied neurobiology · 2022Article
- Interactome overlap between risk genes of epilepsy and targets of anti-epileptic drugs.PloS one · 2022Article
- Article
- Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.Journal of neurology, neurosurgery, and psychiatry · 2021Observational
- "Omics" in traumatic brain injury: novel approaches to a complex disease.Acta neurochirurgica · 2021Review
- Gene Editing and Modulation: the Holy Grail for the Genetic Epilepsies?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Separating the Wheat from the Chaff: The Use of Upstream Regulator Analysis to Identify True Differential Expression of Single Genes within Transcriptomic Datasets.International journal of molecular sciences · 2021Article
- A Transcriptome-Based Drug Discovery Paradigm for Neurodevelopmental Disorders.Annals of neurology · 2021Article
- Using common genetic variants to find drugs for common epilepsies.Brain communications · 2021Article
- Investigating rare and ultrarare epilepsy syndromes withFaculty reviews · 2021Review
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundThe relationship between monogenic and polygenic forms of epilepsy is poorly understood and the extent to which the genetic and acquired epilepsies share common pathways is unclear. Here, we use an integrated systems-level analysis of brain gene expression data to identify molecular networks disrupted in epilepsy.
resultsWe identified a co-expression network of 320 genes (M30), which is significantly enriched for non-synonymous de novo mutations ascertained from patients with monogenic epilepsy and for common variants associated with polygenic epilepsy. The genes in the M30 network are expressed widely in the human brain under tight developmental control and encode physically interacting proteins involved in synaptic processes. The most highly connected proteins within the M30 network were preferentially disrupted by deleterious de novo mutations for monogenic epilepsy, in line with the centrality-lethality hypothesis. Analysis of M30 expression revealed consistent downregulation in the epileptic brain in heterogeneous forms of epilepsy including human temporal lobe epilepsy, a mouse model of acquired temporal lobe epilepsy, and a mouse model of monogenic Dravet (SCN1A) disease. These results suggest functional disruption of M30 via gene mutation or altered expression as a convergent mechanism regulating susceptibility to epilepsy broadly. Using the large collection of drug-induced gene expression data from Connectivity Map, several drugs were predicted to preferentially restore the downregulation of M30 in epilepsy toward health, most notably valproic acid, whose effect on M30 expression was replicated in neurons.
conclusionsTaken together, our results suggest targeting the expression of M30 as a potential new therapeutic strategy in epilepsy.
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