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  Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Steffens, M., Leu, C., Ruppert, A. K., Zara, F., Striano, P., Robbiano, A., et al. (2012). Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Human Molecular Genetics, 21(24), 5359-5372. doi:10.1093/hmg/dds373.

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© The Author(s) 2012. Published by Oxford University Press.




Steffens, M., Author
Leu, C., Author
Ruppert, A. K., Author
Zara, F., Author
Striano, P., Author
Robbiano, A., Author
Capovilla, G., Author
Tinuper, P., Author
Gambardella, A., Author
Bianchi, A., Author
La Neve, A., Author
Crichiutti, G., Author
de Kovel, Author
Kasteleijn-Nolst Trenite, D., Author
de Haan, Author
Lindhout, D., Author
Gaus, V., Author
Schmitz, B., Author
Janz, D., Author
Weber, Y. G., Author
Becker, F., AuthorLerche, H., AuthorSteinhoff, B. J., AuthorKleefuss-Lie, A. A., AuthorKunz, W. S., AuthorSurges, R., AuthorElger, C. E., AuthorMuhle, H., Authorvon Spiczak, S., AuthorOstertag, P., AuthorHelbig, I., AuthorStephani, U., AuthorMoller, R. S., AuthorHjalgrim, H., AuthorDibbens, L. M., AuthorBellows, S., AuthorOliver, K., AuthorMullen, S., AuthorScheffer, I. E., AuthorBerkovic, S. F., AuthorEverett, K. V., AuthorGardiner, M. R., AuthorMarini, C., AuthorGuerrini, R., AuthorLehesjoki, A. E., AuthorSiren, A., AuthorGuipponi, M., AuthorMalafosse, A., AuthorThomas, P., AuthorNabbout, R., AuthorBaulac, S., AuthorLeguern, E., AuthorGuerrero, R., AuthorSerratosa, J. M., AuthorReif, P. S., AuthorRosenow, F., AuthorMorzinger, M., AuthorFeucht, M., AuthorZimprich, F., AuthorKapser, C., AuthorSchankin, C. J., AuthorSuls, A., AuthorSmets, K., AuthorDe Jonghe, P., AuthorJordanova, A., AuthorCaglayan, H., AuthorYapici, Z., AuthorYalcin, D. A., AuthorBaykan, B., AuthorBebek, N., AuthorOzbek, U., AuthorGieger, C., AuthorWichmann, H. E., AuthorBalschun, T., AuthorEllinghaus, D., AuthorFranke, A., AuthorMeesters, C., AuthorBecker, T., AuthorWienker, T. F.1, 2, Author              Hempelmann, A., AuthorSchulz, H., AuthorRuschendorf, F., AuthorLeber, M., AuthorPauck, S. M., AuthorTrucks, H., AuthorToliat, M. R., AuthorNurnberg, P., AuthorAvanzini, G., AuthorKoeleman, B. P., AuthorSander, T., Author more..
1Clinical Genetics (Thomas F. Wienker), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479643              
2Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany, ou_persistent22              


Free keywords: -
 Abstract: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 x 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 x 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 x 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 x 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 x 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.


Language(s): eng - English
 Dates: 2012-09-042012-12-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1093/hmg/dds373
 Degree: -



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Title: Human Molecular Genetics
Source Genre: Journal
Publ. Info: Oxford, England : IRL Press
Pages: - Volume / Issue: 21 (24) Sequence Number: - Start / End Page: 5359 - 5372 Identifier: ISSN: 0964-6906
CoNE: https://pure.mpg.de/cone/journals/resource/954925581153