Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes

L Skotte; J Fadista; J Bybjerg-Grauholm; V Appadurai; MS Hildebrand; TF Hansen; K Banasik; J Grove; C Albiñana; F Geller; CF Bjurström; BJ Vilhjálmsson; M Coleman; JA Damiano; R Burgess; IE Scheffer; OBV Pedersen; C Erikstrup; D Westergaard; KR Nielsen; E Sørensen; MT Bruun; X Liu; H Hjalgrim; TH Pers; PB Mortensen; O Mors; M Nordentoft; JW Dreier; AD Børglum; J Christensen; DM Hougaard; A Buil; A Hviid; M Melbye; H Ullum; SF Berkovic; T Werge; B Feenstra

Journal article

Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes

L Skotte, J Fadista, J Bybjerg-Grauholm, V Appadurai, MS Hildebrand, TF Hansen, K Banasik, J Grove, C Albiñana, F Geller, CF Bjurström, BJ Vilhjálmsson, M Coleman, JA Damiano, R Burgess, IE Scheffer, OBV Pedersen, C Erikstrup, D Westergaard, KR Nielsen Show all

Brain | OXFORD UNIV PRESS | Published : 2022

DOI: 10.1093/brain/awab260

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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 o..

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University of Melbourne Researchers

Michael Hildebrand Author

Matt Coleman Author

Ingrid Scheffer Author

Sam Berkovic Author

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Grants

Awarded by Danish Medical Research Council

Awarded by Oak Foundation

Awarded by US National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases

Awarded by Novo Nordisk Foundation Challenge programme

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Lundbeck Foundation Ascending Investigator grant

Awarded by R.D Wright Career Development Fellowship

Awarded by Carlsberg Foundation postdoctoral fellowship

Awarded by Novo Nordisk Foundation

Awarded by Lundbeck Foundation

Funding Acknowledgements

The study was supported by grants from the Danish Medical Research Council (0602-01818B), the Oak Foundation (OCAY-18598), the US National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (R01AI093697), the Novo Nordisk Foundation Challenge programme (NNF17OC0027594), a Lundbeck Foundation Ascending Investigator grant (R313-2019-554) to B.F., and National Health and Medical Research Council (NHMRC) Program Grant (1091593) to S.F.B. and I.E.S, Practitioner Fellowship (1006110) to I.E.S., and R.D Wright Career Development Fellowship (1063799) to M.S.H., and a Novo Nordisk Foundation Hallas-Moller grant to A.H. The Danish National Biobank was established with the support of major grants from the Novo Nordisk Foundation, the Danish Medical Research Council and the Lundbeck Foundation. L.S. received support from a Carlsberg Foundation postdoctoral fellowship (CF15-0899); X.L. reports funding from the Nordic Center of Excellence in Health-Related e-Sciences; K.B. received support from the Novo Nordisk Foundation (NNF14CC0001, NNF17OC0027594); D.W. reports funding from the Novo Nordisk Foundation (NNF18SA0034956, NNF14CC0001, NNF17OC0027594); T.H.P. acknowledges the Novo Nordisk Foundation (NNF18CC0034900) and the Lundbeck Foundation (R190-2014-3904); J.C. and J.W.D. report funding from the Novo Nordisk Foundation (NNF16OC0019126), The Danish Epilepsy Association and the Central Denmark Region; C.A. is supported by The Danish National Research Foundation (Niels Bohr Professorship to John McGrath). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.