Stefan Wolking, Herbert Schulz, Anne T, Nies, Mark McCormack, Elke Schäffeler, Pauls Auce, Andreja Avbersek, Felicitas Becker, Karl Martin Klein, Martin Krenn, Rikke S. Møller, Marina Nikanorova, Sarah Weckhuysen, Gianpiero L. Cavalleri, Norman Delanty, Chantal Depondt, Michael R. Johnson, Bobby P. C. Koeleman, Wolfram S. Kunz, Anthony G. Marson, Josemir W. Sander, Graeme J. Sills, Pasquale Striano, Federico J. Zara, Fritz Zimprich, Yvonne G. Weber, Roland Krause, Sanjay M. Sisodiya, Matthias Schwab, Thomas Sander, Holger Lerche
- Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
Metadaten| Author: | Stefan Wolking, Herbert Schulz, Anne T, Nies, Mark McCormack, Elke Schäffeler, Pauls Auce, Andreja Avbersek, Felicitas Becker, Karl Martin KleinORCiD, Martin Krenn, Rikke S. MøllerORCiDGND, Marina Nikanorova, Sarah Weckhuysen, Gianpiero L. CavalleriORCiD, Norman Delanty, Chantal Depondt, Michael R. Johnson, Bobby P. C. Koeleman, Wolfram S. Kunz, Anthony G. Marson, Josemir W. Sander, Graeme J. Sills, Pasquale StrianoORCiDGND, Federico J. ZaraORCiD, Fritz ZimprichORCiDGND, Yvonne G. Weber, Roland Krause, Sanjay M. SisodiyaORCiD, Matthias Schwab, Thomas Sander, Holger LercheORCiDGND |
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| URN: | urn:nbn:de:hebis:30:3-547170 |
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| DOI: | https://doi.org/10.2217/pgs-2019-0179 |
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| ISSN: | 1744-8042 |
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| ISSN: | 1462-2416 |
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| Parent Title (English): | Pharmacogenomics |
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| Publisher: | Future Medicine |
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| Place of publication: | London |
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| Document Type: | Article |
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| Language: | English |
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| Date of Publication (online): | 2020/04/20 |
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| Date of first Publication: | 2020/04/20 |
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| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Contributing Corporation: | EpiPGx Consortium |
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| Release Date: | 2020/10/27 |
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| Tag: | GWAS; antiepileptic drugs; genetic generalized epilepsy; lamotrigine; levetiracetam; pharmacoresistance; valproic acid |
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| Volume: | 21 |
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| Issue: | 5 |
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| Page Number: | 11 |
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| First Page: | 325 |
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| Last Page: | 335 |
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| HeBIS-PPN: | 472986511 |
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| Institutes: | Medizin / Medizin |
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| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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| Sammlungen: | Universitätspublikationen |
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| Licence (German): |  Deutsches Urheberrecht |
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