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Genome-wide associa...
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Skotte, LineDanish Serum Institute, Copenhagen
(author)
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-01-12
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Oxford University Press (OUP),2022
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14 s.
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:781b7c00-bd3b-48cb-a379-b3a4d725c9d7
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https://lup.lub.lu.se/record/781b7c00-bd3b-48cb-a379-b3a4d725c9d7URI
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https://doi.org/10.1093/brain/awab260DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Fadista, JoãoLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Danish Serum Institute, Copenhagen,University of Helsinki(Swepub:lu)med-jft
(author)
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Bybjerg-Grauholm, JonasDanish Serum Institute, Copenhagen
(author)
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Appadurai, Vivek
(author)
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Hildebrand, Michael S.Murdoch Children's Research Institute,University of Melbourne
(author)
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Hansen, Thomas F.Copenhagen University Hospital,University of Copenhagen
(author)
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Banasik, KarinaUniversity of Copenhagen
(author)
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Grove, JakobAarhus University
(author)
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Albiñana, ClaraAarhus University
(author)
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Geller, FrankDanish Serum Institute, Copenhagen
(author)
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Bjurström, Carmen F.Danish Serum Institute, Copenhagen
(author)
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Vilhjálmsson, Bjarni J.Aarhus University
(author)
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Coleman, MatthewMurdoch Children's Research Institute,University of Melbourne
(author)
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Damiano, John A.University of Melbourne
(author)
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Burgess, RosemaryUniversity of Melbourne
(author)
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Scheffer, Ingrid E.University of Melbourne,The Florey Institute of Neuroscience and Mental Health
(author)
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Pedersen, Ole Birger VesteragerZealand University Hospital
(author)
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Erikstrup, ChristianAarhus University Hospital
(author)
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Westergaard, DavidUniversity of Copenhagen
(author)
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Nielsen, Kaspar RenéAalborg University Hospital
(author)
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Sørensen, ErikCopenhagen University Hospital
(author)
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Bruun, Mie TopholmOdense University Hospital
(author)
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Liu, XuepingDanish Serum Institute, Copenhagen
(author)
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Hjalgrim, HenrikCopenhagen University Hospital,University of Copenhagen,Danish Serum Institute, Copenhagen
(author)
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Pers, Tune H.University of Copenhagen
(author)
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Mortensen, Preben BoAarhus University
(author)
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Mors, OleAarhus University Hospital
(author)
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Nordentoft, MereteUniversity of Copenhagen
(author)
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Dreier, Julie W.Aarhus University
(author)
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Børglum, Anders D.Aarhus University
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Christensen, JakobAarhus University,Aarhus University Hospital
(author)
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Hougaard, David M.Danish Serum Institute, Copenhagen
(author)
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Buil, Alfonso
(author)
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Hviid, AndersDanish Serum Institute, Copenhagen,University of Copenhagen
(author)
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Melbye, MadsStanford University School of Medicine,Danish Serum Institute, Copenhagen,University of Copenhagen
(author)
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Ullum, HenrikCopenhagen University Hospital,Danish Serum Institute, Copenhagen
(author)
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Berkovic, Samuel F.University of Melbourne
(author)
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Werge, Thomas
(author)
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Feenstra, BjarkeDanish Serum Institute, Copenhagen
(author)
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Danish Serum Institute, CopenhagenTranslationell muskelforskning
(creator_code:org_t)
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In:Brain: Oxford University Press (OUP)145:2, s. 555-5680006-89501460-2156
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Skotte, Line
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Fadista, João
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Bybjerg-Grauholm ...
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Appadurai, Vivek
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Hildebrand, Mich ...
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Hansen, Thomas F ...
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Banasik, Karina
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Grove, Jakob
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Albiñana, Clara
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Geller, Frank
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Bjurström, Carme ...
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Vilhjálmsson, Bj ...
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Coleman, Matthew
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Damiano, John A.
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Scheffer, Ingrid ...
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Pedersen, Ole Bi ...
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Erikstrup, Chris ...
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Westergaard, Dav ...
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Nielsen, Kaspar ...
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Sørensen, Erik
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Bruun, Mie Topho ...
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Liu, Xueping
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Hjalgrim, Henrik
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Pers, Tune H.
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Mortensen, Prebe ...
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Mors, Ole
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Nordentoft, Mere ...
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Dreier, Julie W.
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Børglum, Anders ...
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Christensen, Jak ...
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Buil, Alfonso
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Hviid, Anders
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Melbye, Mads
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