ArticleAmerican journal of human genetics2012
Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies.PloS one · 2017Pooled it
- Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies.The Lancet. Neurology · 2014Pooled it
- Article
- Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.Neurogenetics · 2024Article
- Genetics of Epileptic Networks: from Focal to Generalized Genetic Epilepsies.Current neurology and neuroscience reports · 2020Review
- Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Article
- Genetics and Extracellular Vesicles of Pediatrics Sleep Disordered Breathing and Epilepsy.International journal of molecular sciences · 2019Review
- Phenotypic variability of GABRA1-related epilepsy in monozygotic twins.Annals of clinical and translational neurology · 2019Article
- Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals.American journal of human genetics · 2019Article
- Targeted resequencing identifies genes with recurrent variation in cerebral palsy.NPJ genomic medicine · 2019Article
- Subtle Brain Developmental Abnormalities in the Pathogenesis of Juvenile Myoclonic Epilepsy.Frontiers in cellular neuroscience · 2019Review
- Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes.Neurogenetics · 2018Article
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.PloS one · 2018Article
- GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant.Neurobiology of disease · 2017Article
- Functional variants inEpilepsia open · 2017Article
- Genetic and epigenetic mechanisms of epilepsy: a review.Neuropsychiatric disease and treatment · 2017Review
- Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.European journal of human genetics : EJHG · 2016Article
- Mutation of orthologous prickle genes causes a similar epilepsy syndrome in flies and humans.Annals of clinical and translational neurology · 2016Article
- Identification of genetic variants associated with susceptibility to West Nile virus neuroinvasive disease.Genes and immunity · 2016Article
Corrections and comments
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Authors and funding
30 authors at 7 institutions in 4 countries.
Funding
Abstract
Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little is known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals with IGE; however, it remains unclear whether variants with moderate effect size and frequencies below what are reliably detected with genome-wide association studies contribute significantly to disease risk. In this study, we compare the exome sequences of 118 individuals with IGE and 242 controls of European ancestry by using next-generation sequencing. The exome-sequenced epilepsy cases include study subjects with two forms of IGE, including juvenile myoclonic epilepsy (n = 93) and absence epilepsy (n = 25). However, our discovery strategy did not assume common genetic control between the subtypes of IGE considered. In the sequence data, as expected, no variants were significantly associated with the IGE phenotype or more specific IGE diagnoses. We then selected 3,897 candidate epilepsy-susceptibility variants from the sequence data and genotyped them in a larger set of 878 individuals with IGE and 1,830 controls. Again, no variant achieved statistical significance. However, 1,935 variants were observed exclusively in cases either as heterozygous or homozygous genotypes. It is likely that this set of variants includes real risk factors. The lack of significant association evidence of single variants with disease in this two-stage approach emphasizes the high genetic heterogeneity of epilepsy disorders, suggests that the impact of any individual single-nucleotide variant in this disease is small, and indicates that gene-based approaches might be more successful for future sequencing studies of epilepsy predisposition.
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