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Genome-wide associa...
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
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- Skotte, Line (författare)
- Danish Serum Institute, Copenhagen
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- Fadista, João (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Danish Serum Institute, Copenhagen,University of Helsinki
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- Bybjerg-Grauholm, Jonas (författare)
- Danish Serum Institute, Copenhagen
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Appadurai, Vivek (författare)
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- Hildebrand, Michael S. (författare)
- Murdoch Children's Research Institute,University of Melbourne
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- Hansen, Thomas F. (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Banasik, Karina (författare)
- University of Copenhagen
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- Grove, Jakob (författare)
- Aarhus University
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- Albiñana, Clara (författare)
- Aarhus University
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- Geller, Frank (författare)
- Danish Serum Institute, Copenhagen
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- Bjurström, Carmen F. (författare)
- Danish Serum Institute, Copenhagen
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- Vilhjálmsson, Bjarni J. (författare)
- Aarhus University
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- Coleman, Matthew (författare)
- Murdoch Children's Research Institute,University of Melbourne
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- Damiano, John A. (författare)
- University of Melbourne
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- Burgess, Rosemary (författare)
- University of Melbourne
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- Scheffer, Ingrid E. (författare)
- University of Melbourne,The Florey Institute of Neuroscience and Mental Health
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- Pedersen, Ole Birger Vesterager (författare)
- Zealand University Hospital
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- Erikstrup, Christian (författare)
- Aarhus University Hospital
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- Westergaard, David (författare)
- University of Copenhagen
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- Nielsen, Kaspar René (författare)
- Aalborg University Hospital
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- Sørensen, Erik (författare)
- Copenhagen University Hospital
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- Bruun, Mie Topholm (författare)
- Odense University Hospital
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- Liu, Xueping (författare)
- Danish Serum Institute, Copenhagen
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- Hjalgrim, Henrik (författare)
- Copenhagen University Hospital,University of Copenhagen,Danish Serum Institute, Copenhagen
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- Pers, Tune H. (författare)
- University of Copenhagen
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- Mortensen, Preben Bo (författare)
- Aarhus University
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- Mors, Ole (författare)
- Aarhus University Hospital
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- Nordentoft, Merete (författare)
- University of Copenhagen
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- Dreier, Julie W. (författare)
- Aarhus University
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- Børglum, Anders D. (författare)
- Aarhus University
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- Christensen, Jakob (författare)
- Aarhus University,Aarhus University Hospital
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- Hougaard, David M. (författare)
- Danish Serum Institute, Copenhagen
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Buil, Alfonso (författare)
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- Hviid, Anders (författare)
- Danish Serum Institute, Copenhagen,University of Copenhagen
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- Melbye, Mads (författare)
- Stanford University School of Medicine,Danish Serum Institute, Copenhagen,University of Copenhagen
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- Ullum, Henrik (författare)
- Copenhagen University Hospital,Danish Serum Institute, Copenhagen
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- Berkovic, Samuel F. (författare)
- University of Melbourne
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Werge, Thomas (författare)
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- Feenstra, Bjarke (författare)
- Danish Serum Institute, Copenhagen
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(creator_code:org_t)
- 2022-01-12
- 2022
- Engelska 14 s.
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- epilepsy
- febrile seizures
- fever response genes
- genome-wide association study
- neuronal excitability genes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Brain
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- Av författaren/redakt...
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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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visa fler...
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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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Burgess, Rosemar ...
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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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Hougaard, David ...
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Buil, Alfonso
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Hviid, Anders
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Melbye, Mads
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Ullum, Henrik
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Berkovic, Samuel ...
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Werge, Thomas
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Feenstra, Bjarke
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