Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Wolking, S and Moreau, C and Nies, AT and Schaeffeler, E and McCormack, M and Auce, P and Avbersek, A and Becker, F and Krenn, M and Møller, RS and Nikanorova, M and Weber, YG and Weckhuysen, S and Cavalleri, GL and Delanty, N and Depondt, C and Johnson, MR and Koeleman, BPC and Kunz, WS and Marson, AG and Sander, JW and Sills, GJ and Striano, P and Zara, F and Zimprich, F and Schwab, M and Krause, R and Sisodiya, SM and Cossette, P and Girard, SL and Lerche, H and EpiPGX, Consortium},
doi = {10.1111/epi.16467},
journal = {Epilepsia},
pages = {657--666},
title = {Testing association of rare genetic variants with resistance to three common antiseizure medications},
url = {},
volume = {61},
year = {2020}

RIS format (EndNote, RefMan)

AB - OBJECTIVE: Drug resistance is a major concern in the treatment of individuals with epilepsy. No genetic markers for resistance to individual antiseizure medication (ASM) have yet been identified. We aimed to identify the role of rare genetic variants in drug resistance for three common ASMs: levetiracetam (LEV), lamotrigine (LTG), and valproic acid (VPA). METHODS: A cohort of 1622 individuals of European descent with epilepsy was deeply phenotyped and underwent whole exome sequencing (WES), comprising 575 taking LEV, 826 LTG, and 782 VPA. We performed gene- and gene set-based collapsing analyses comparing responders and nonresponders to the three drugs to determine the burden of different categories of rare genetic variants. RESULTS: We observed a marginally significant enrichment of rare missense, truncating, and splice region variants in individuals who were resistant to VPA compared to VPA responders for genes involved in VPA pharmacokinetics. We also found a borderline significant enrichment of truncating and splice region variants in the synaptic vesicle glycoprotein (SV2) gene family in nonresponders compared to responders to LEV. We did not see any significant enrichment using a gene-based approach. SIGNIFICANCE: In our pharmacogenetic study, we identified a slightly increased burden of damaging variants in gene groups related to drug kinetics or targeting in individuals presenting with drug resistance to VPA or LEV. Such variants could thus determine a genetic contribution to drug resistance.
AU - Wolking,S
AU - Moreau,C
AU - Nies,AT
AU - Schaeffeler,E
AU - McCormack,M
AU - Auce,P
AU - Avbersek,A
AU - Becker,F
AU - Krenn,M
AU - Møller,RS
AU - Nikanorova,M
AU - Weber,YG
AU - Weckhuysen,S
AU - Cavalleri,GL
AU - Delanty,N
AU - Depondt,C
AU - Johnson,MR
AU - Koeleman,BPC
AU - Kunz,WS
AU - Marson,AG
AU - Sander,JW
AU - Sills,GJ
AU - Striano,P
AU - Zara,F
AU - Zimprich,F
AU - Schwab,M
AU - Krause,R
AU - Sisodiya,SM
AU - Cossette,P
AU - Girard,SL
AU - Lerche,H
AU - EpiPGX,Consortium
DO - 10.1111/epi.16467
EP - 666
PY - 2020///
SN - 0013-9580
SP - 657
TI - Testing association of rare genetic variants with resistance to three common antiseizure medications
T2 - Epilepsia
UR -
UR -
UR -
UR -
VL - 61
ER -