$ R) |7 U g# V& ^% ddoi:10.1038/ng.3129 : j$ W6 h0 Y- G2 [; U* V( MPMC: 3 X) F& T) T% u$ @5 N& z: iPMID:; s$ i z- s' }2 J& n" p* \! w+ E9 f
' O' k* y: R0 kCommon variants associated with general and MMR vaccine–related febrile seizures ; B( Z5 k4 V V1 c4 ~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 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. $ a" B8 U& x" Y0 a& F/ y+ ]% N. x
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