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Nat Genet. 2014 Dec;46(12):1274-82. doi: 10.1038/ng.3129. Epub 2014 Oct 26.

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

Author information

1
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
2
1] Department of Physiology, University of California, San Francisco, San Francisco, California, USA. [2] Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA. [3] Howard Hughes Medical Institute, San Francisco, California, USA.
3
Department of Microbiology, University of Texas Southwestern Medical School, Dallas, Texas, USA.
4
Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
5
Research Unit and Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
6
1] Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. [2] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. [3] Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

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(-12) versus controls, P = 1.2 × 10(-9) versus MMR-unrelated febrile seizures) and the measles virus receptor CD46 (rs1318653: P = 9.6 × 10(-11) versus controls, P = 1.6 × 10(-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(-16)) and SCN2A (rs3769955: P = 3.1 × 10(-10)), a TMEM16 family gene (ANO3; rs114444506: P = 3.7 × 10(-20)) and a region associated with magnesium levels (12q21.33; rs11105468: P = 3.4 × 10(-11)). Finally, we show the functional relevance of ANO3 (TMEM16C) with electrophysiological experiments in wild-type and knockout rats.

Comment in

PMID:
25344690
PMCID:
PMC4244308
DOI:
10.1038/ng.3129
[Indexed for MEDLINE]
Free PMC Article

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