Wolking, S;
Campbell, C;
Stapleton, C;
McCormack, M;
Delanty, N;
Depondt, C;
Johnson, MR;
... Lerche, H; + view all
(2021)
Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications.
Frontiers in Pharmacology
, 12
, Article 688386. 10.3389/fphar.2021.688386.
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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
| Type: | Article |
|---|---|
| Title: | Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fphar.2021.688386 |
| Publisher version: | https://doi.org/10.3389/fphar.2021.688386 |
| Language: | English |
| Additional information: | © 2021 Wolking, Campbell, Stapleton, McCormack, Delanty, Depondt, Johnson, Koeleman, Krause, Kunz, Marson, Sander, Sills, Striano, Zara, Sisodiya, Cavalleri, Lerche and EpiPGX Consortium. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | drug-resistant epilepsies, polygenic risk score (PRS), GWAS, anti-seizure medication (ASM), single nucelotide polymorphisms |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10130813 |
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