Role of common genetic variants for drug-resistance to specific anti-seizure medications
Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation.
Methods: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance.
Results: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs.
Significance: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scale.
FP7 grant 279062 “EpiPGX” from the European Commission
German Research Foundation (DFG) (WO 2385/1-1)
CommentsThe original article is available at https://www.frontiersin.org
Published CitationWolking S, et al. Role of common genetic variants for drug-resistance to specific anti-seizure medications. Front Pharmacol. 2021;12:688386.
Publication Date9 June 2021
- Beaumont Hospital
- FutureNeuro Centre
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
PublisherFrontiers Media SA
- Published Version (Version of Record)