ArticleNature neuroscience2024
Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.
Article in Nature neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Gene burden meta-analysis of 748 879 individuals identifies LGI1-ADAM23 protein complex association with epilepsy.Epilepsia · 2026Pooled it
- Genome-wide association meta-analyses of drug-resistant epilepsy.EBioMedicine · 2025Pooled it
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- Mosaic human cortical organoids model mTOR-related focal cortical dysplasia through DEPDC5 deletion.Brain : a journal of neurology · 2026Article
- Shared molecular pathways in pediatric genetic epilepsies: Insights from a single-center cohort of 80 patients.Epilepsia open · 2026Article
- Beyond Seizure Management in a Developmental Epileptic Encephalopathy: Expanding the SLC6A1 Neurodevelopmental Disorder Phenotype.Neurology. Genetics · 2026Article
- Ras-MAPK somatic variants in mesial temporal lobe epilepsy.Current opinion in genetics & development · 2026Review
- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- The Global Parkinson's Disease Genetics (GP2) Genome Browser.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Rare genetic variation in adults with surgically treated temporal lobe epilepsy: An exome sequencing study.Epilepsia open · 2026Article
- Convergent coexpression reveals shared biological mechanisms underlying common and rare variant risk in six neuropsychiatric disorders.Molecular psychiatry · 2026Article
- Low diagnostic yield of presurgical genetic testing in adult patients with epilepsy.Epilepsia · 2026Article
- A translational multimodal machine-learning prototype predicting valproate response in epilepsy treatment.Epilepsia · 2026Article
- Review
- [Associations Between Genetic Causes of Psychiatric Disorders and Rare Monogenic Epilepsies].Der Nervenarzt · 2026Review
- Scaling of Neuronal Growth and Excitability Through Separable mTORC1 and mTORC2 Pathways.bioRxiv : the preprint server for biology · 2026Article
- Multi-Omics Dissection of the Shared Genetic Architecture Between Sleep Traits and Epilepsy.Biology · 2026Article
- Genomic Profiling of Adults with Pharmacoresistant Genetic Generalized Epilepsy.Brain sciences · 2026Article
- Mapping the heritability of disease: a nationwide study.Nature communications · 2026Article
- A Comprehensive Overview of the Clinical, Electrophysiological, and Neuroimaging Features of BPAN: Insights From a New Case Series.Annals of clinical and translational neurology · 2026Article
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Abstract
Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies.
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