{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:31:35Z","timestamp":1789439495381,"version":"build-2803163510"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008392","name":"Danish Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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 &amp;lt; 5 \u00d7 10\u221210.<\/jats:p>\n                  <jats:p>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 \u00d7 10\u22124). 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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1093\/brain\/awab260","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T15:14:18Z","timestamp":1625843658000},"page":"555-568","source":"Crossref","is-referenced-by-count":65,"title":["Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes"],"prefix":"10.1093","volume":"145","author":[{"given":"Line","family":"Skotte","sequence":"first","affiliation":[{"name":"Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Fadista","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark"},{"name":"Department of Clinical Sciences, Lund University Diabetes Centre, Malm\u00f6, Sweden"},{"name":"Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Bybjerg-Grauholm","sequence":"additional","affiliation":[{"name":"Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark"},{"name":"iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Appadurai","sequence":"additional","affiliation":[{"name":"iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark"},{"name":"Mental Health Center Sct. 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