Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study.
Stefan WolkingHerbert SchulzAnne T NiesMark McCormackElke SchaeffelerPauls AuceAndreja AvbersekFelicitas BeckerKarl M KleinMartin KrennRikke S MøllerMarina NikanorovaSarah WeckhuysenEpiPGx ConsortiumGianpiero L CavalleriNorman DelantyChantal DepondtMichael R JohnsonBobby Pc KoelemanWolfram S KunzAnthony G MarsonJosemir W SanderGraeme J SillsPasquale StrianoFederico ZaraFritz ZimprichYvonne G WeberRoland KrauseSanjay SisodiyaMatthias SchwabThomas SanderHolger LerchePublished in: Pharmacogenomics (2020)
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.