作者
Stefan Wolking,Herbert Schulz,Anne A.T. Nies,Mark McCormack,Elke Schaeffeler,Pauls Auce,Andreja Avberšek,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 W.S. Kunz,Anthony G Marson,Josemir W. Sander,Graeme J. Sills,Pasquale Striano,Federico Zara,Fritz Zimprich,Yvonne Weber,Roland Krause,Sanjay M. Sisodiya,Matthias Schwab,Thomas Sander,Holger Lerche
摘要
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.