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.
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