Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications

Wolking, Stefan, Campbell, Ciaran, Stapleton, Caragh, McCormack, Mark, Delanty, Norman, Depondt, Chantal, Johnson, Michael R, Koeleman, Bobby PC, Krause, Roland, Kunz, Wolfram S
et al (show 8 more authors) (2021) Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications. FRONTIERS IN PHARMACOLOGY, 12. 688386-.

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<b>Objective:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Significance:</b> 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.

Item Type: Article
Uncontrolled Keywords: drug-resistant epilepsies, polygenic risk score (PRS), GWAS, anti-seizure medication (ASM), single nucelotide polymorphisms
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Jan 2022 09:37
Last Modified: 18 Jan 2023 21:14
DOI: 10.3389/fphar.2021.688386
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