Common variants associated with general and MMR vaccine-related febrile seizures

Bjarke Feenstra, Björn Pasternak, Frank Geller, Lisbeth Carstensen, Tongfei Wang, Fen Huang, Jennifer L. Eitson, Mads V. Hollegaard, Henrik Svanström, Mogens Vestergaard, David M. Hougaard, John W. Schoggins, Lily Yeh Jan, Mads Melbye, Anders Hviid

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Abstract

Febrile seizures represent a serious adverse event following measles, mumps and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures, harboring the interferon-stimulated gene IFI44L (rs273259: P = 5.9 × 10 â '12 versus controls, P = 1.2 × 10 â '9 versus MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653: P = 9.6 × 10 â '11 versus controls, P = 1.6 × 10 â '9 versus MMR-unrelated febrile seizures). Furthermore, four loci were associated with febrile seizures in general, implicating the sodium channel genes SCN1A (rs6432860: P = 2.2 × 10 â '16) and SCN2A (rs3769955: P = 3.1 × 10 â '10), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 × 10 â '20) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10 â '11). Finally, we show the functional relevance of ANO3 (TMEM16C) with electrophysiological experiments in wild-type and knockout rats.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalNature Genetics
Volume46
Issue number12
DOIs
StatePublished - Dec 11 2014

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Measles-Mumps-Rubella Vaccine
Febrile Seizures
Mumps
Rubella
Measles
Vaccination
Genes
Virus Receptors
Measles virus
Sodium Channels
Genome-Wide Association Study
Magnesium
Interferons

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Feenstra, B., Pasternak, B., Geller, F., Carstensen, L., Wang, T., Huang, F., ... Hviid, A. (2014). Common variants associated with general and MMR vaccine-related febrile seizures. Nature Genetics, 46(12), 1274-1282. https://doi.org/10.1038/ng.3129

Common variants associated with general and MMR vaccine-related febrile seizures. / Feenstra, Bjarke; Pasternak, Björn; Geller, Frank; Carstensen, Lisbeth; Wang, Tongfei; Huang, Fen; Eitson, Jennifer L.; Hollegaard, Mads V.; Svanström, Henrik; Vestergaard, Mogens; Hougaard, David M.; Schoggins, John W.; Jan, Lily Yeh; Melbye, Mads; Hviid, Anders.

In: Nature Genetics, Vol. 46, No. 12, 11.12.2014, p. 1274-1282.

Research output: Contribution to journalArticle

Feenstra, B, Pasternak, B, Geller, F, Carstensen, L, Wang, T, Huang, F, Eitson, JL, Hollegaard, MV, Svanström, H, Vestergaard, M, Hougaard, DM, Schoggins, JW, Jan, LY, Melbye, M & Hviid, A 2014, 'Common variants associated with general and MMR vaccine-related febrile seizures', Nature Genetics, vol. 46, no. 12, pp. 1274-1282. https://doi.org/10.1038/ng.3129
Feenstra B, Pasternak B, Geller F, Carstensen L, Wang T, Huang F et al. Common variants associated with general and MMR vaccine-related febrile seizures. Nature Genetics. 2014 Dec 11;46(12):1274-1282. https://doi.org/10.1038/ng.3129
Feenstra, Bjarke ; Pasternak, Björn ; Geller, Frank ; Carstensen, Lisbeth ; Wang, Tongfei ; Huang, Fen ; Eitson, Jennifer L. ; Hollegaard, Mads V. ; Svanström, Henrik ; Vestergaard, Mogens ; Hougaard, David M. ; Schoggins, John W. ; Jan, Lily Yeh ; Melbye, Mads ; Hviid, Anders. / Common variants associated with general and MMR vaccine-related febrile seizures. In: Nature Genetics. 2014 ; Vol. 46, No. 12. pp. 1274-1282.
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