ArticleBrain : a journal of neurology2022
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Genome-wide meta-analyses identify five new risk loci for nonsyndromic orofacial clefts in the Chinese Han population.Molecular genetics & genomic medicine · 2023Pooled it
- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- Febrile Seizures and School Performance.JAMA network open · 2026Article
- Autism-like behavior induced by conditional ablation of the Bassoon gene in GABAergic interneurons.Molecular psychiatry · 2026Article
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Genetic-Epigenetic Interplay in Epilepsy: Pathways, Biomarkers, and Epigenome-Targeted Therapies.Epigenomes · 2026Review
- Article
- Alterations in Gut Microbiota and their Association with Intestinal Mucosal Injury in Children with Febrile Seizures.Neurosciences (Riyadh, Saudi Arabia) · 2026Article
- Increased excitability of layer 5 neocortical pyramidal neurons and its contribution to seizure activity in Gabrg2 gene-deficient mice.iScience · 2026Article
- The genotypic spectrum of complex febrile seizures: insights from high-risk population genetic screening in a pediatric cohort.Frontiers in neuroscience · 2026Article
- Beyond the synapse: Bassoon mutations drive epilepsy through Astrocyte-Neuron crosstalk.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- CRISPR-edited iPSCs reveal BSN gene mutations induce neuronal hyperexcitability via astrocyte lipid accumulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- The risk of epilepsy after neonatal seizures.Developmental medicine and child neurology · 2025Article
- Variants in BSN, encoding the presynaptic protein Bassoon, result in a distinct neurodevelopmental disorder with a broad phenotypic range.American journal of human genetics · 2025Article
- Genome-Wide Association Study Identifying a Novel Gene Related to a History of Febrile Convulsions in Patients With Focal Epilepsy.Journal of clinical neurology (Seoul, Korea) · 2025Article
- Identification of Genetic Variants in Status Epilepticus Associated With Fever.Brain and behavior · 2025Observational
- Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.eLife · 2025Article
- Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse.Frontiers in neurology · 2025Article
- Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample.Risk management and healthcare policy · 2025Article
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39 authors at 11 institutions in 5 countries.
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Abstract
Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
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