Reference : Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications
Scientific journals : Article
Human health sciences : Neurology
Systems Biomedicine
Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications
Wolking, Stefan [> >]
Campbell, Ciarán [> >]
Stapleton, Caragh [> >]
McCormack, Mark [> >]
Delanty, Norman [> >]
Depondt, Chantal [> >]
Johnson, Michael R. [> >]
Koeleman, Bobby P. C. [> >]
Krause, Roland mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
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 [> >]
Frontiers in Pharmacology
Yes (verified by ORBilu)
[en] 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 ; 279062 - EPIPGX - Epilepsy Pharmacogenomics: delivering biomarkers for clinical use

File(s) associated to this reference

Fulltext file(s):

Open access
fphar-12-688386.pdfPublisher postprint855.17 kBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.