학술논문
Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications
Document Type
article
Author
Stefan Wolking; Ciarán Campbell; Caragh Stapleton; Mark McCormack; Norman Delanty; Chantal Depondt; Michael R. Johnson; Bobby P. C. Koeleman; Roland Krause; Wolfram S. Kunz; Anthony G. Marson; Josemir W. Sander; Graeme J. Sills; Pasquale Striano; Federico Zara; Sanjay M. Sisodiya; Gianpiero L. Cavalleri; Holger Lerche; EpiPGX Consortium
Source
Frontiers in Pharmacology, Vol 12 (2021)
Subject
Language
English
ISSN
1663-9812
68884737
68884737
Abstract
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.