| Title: |
Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications |
| Authors: |
Wolking, Stefan; Campbell, Ciarán; Stapleton, Caragh; McCormack, Mark; Delanty, Norman; Depondt, Chantal; Johnson, Michael R.; Koeleman, Bobby P. C.; KRAUSE, Roland; Kunz, Wolfram S.; Marson, Anthony G.; Sander, Josemir W.; Sills, Graeme J.; Striano, Pasquale; Zara, Federico; Sisodiya, Sanjay M.; Cavalleri, Gianpiero L.; Lerche, Holger; Epipgx Consortium |
| Source: |
Frontiers in Pharmacology, 12, 1291 (2021-06-09) |
| Publisher Information: |
Frontiers |
| Publication Year: |
2021 |
| Collection: |
University of Luxembourg: ORBilu - Open Repository and Bibliography |
| Subject Terms: |
Human health sciences; Neurology; Sciences de la santé humaine; Neurologie |
| Description: |
peer reviewed ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
info:eu-repo/grantAgreement/EC/FP7/279062; https://www.frontiersin.org/article/10.3389/fphar.2021.688386; urn:issn:1663-9812; https://orbilu.uni.lu/handle/10993/47443; info:hdl:10993/47443; info:pmid:34177598; wos:000664641200001 |
| DOI: |
10.3389/fphar.2021.688386 |
| Availability: |
https://orbilu.uni.lu/handle/10993/47443; https://orbilu.uni.lu/bitstream/10993/47443/1/fphar-12-688386.pdf; https://doi.org/10.3389/fphar.2021.688386 |
| Rights: |
open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.C378C44E |
| Database: |
BASE |