Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study

Stefan Wolking; Herbert Schulz; Anne T Nies; Mark McCormack; Elke Schaeffeler; Pauls Auce; Andreja Avbersek; Felicitas Becker; Karl M Klein; Martin Krenn; Rikke S Møller; Marina Nikanorova; Sarah Weckhuysen; EpiPGx Consortium; Gianpiero L Cavalleri; Norman Delanty; Chantal Depondt; Michael R Johnson; Bobby Pc Koeleman; Wolfram S Kunz; Anthony G Marson; Josemir W Sander; Graeme J Sills; Pasquale Striano; Federico Zara; Fritz Zimprich; Yvonne G Weber; Roland Krause; Sanjay Sisodiya; Matthias Schwab; Thomas Sander; Holger Lerche

doi:10.2217/pgs-2019-0179

Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study

Stefan Wolking^*, Herbert Schulz, Anne T Nies, Mark McCormack, Elke Schaeffeler, Pauls Auce, Andreja Avbersek, Felicitas Becker, Karl M Klein, Martin Krenn, Rikke S Møller, Marina Nikanorova, Sarah Weckhuysen, EpiPGx Consortium, Gianpiero L Cavalleri, Norman Delanty, Chantal Depondt, Michael R Johnson, Bobby Pc Koeleman, Wolfram S KunzAnthony G Marson, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Fritz Zimprich, Yvonne G Weber, Roland Krause, Sanjay Sisodiya, Matthias Schwab, Thomas Sander, Holger Lerche

^*Corresponding author af dette arbejde

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Publikation: Bidrag til tidsskrift › Artikel › Forskning › peer review

Abstract

Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.

Originalsprog	Engelsk
Sider (fra-til)	325-335
Antal sider	11
Tidsskrift	Pharmacogenomics
Vol/bind	21
Udgave nummer	5
Tidlig onlinedato	20 apr. 2020
DOI	https://doi.org/10.2217/pgs-2019-0179
Status	Udgivet - apr. 2020

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10.2217/pgs-2019-0179

Citationsformater

Wolking, S., Schulz, H., Nies, A. T., McCormack, M., Schaeffeler, E., Auce, P., Avbersek, A., Becker, F., Klein, K. M., Krenn, M., Møller, R. S., Nikanorova, M., Weckhuysen, S., Consortium, EG., Cavalleri, G. L., Delanty, N., Depondt, C., Johnson, M. R., Koeleman, B. P., ... Lerche, H. (2020). Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study. Pharmacogenomics, 21(5), 325-335. https://doi.org/10.2217/pgs-2019-0179

@article{e3c0e092d18e4f148924adeab54bedd7,

title = "Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study",

abstract = "Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.",

author = "Stefan Wolking and Herbert Schulz and Nies, {Anne T} and Mark McCormack and Elke Schaeffeler and Pauls Auce and Andreja Avbersek and Felicitas Becker and Klein, {Karl M} and Martin Krenn and M{\o}ller, {Rikke S} and Marina Nikanorova and Sarah Weckhuysen and EpiPGx Consortium and Cavalleri, {Gianpiero L} and Norman Delanty and Chantal Depondt and Johnson, {Michael R} and Koeleman, {Bobby Pc} and Kunz, {Wolfram S} and Marson, {Anthony G} and Sander, {Josemir W} and Sills, {Graeme J} and Pasquale Striano and Federico Zara and Fritz Zimprich and Weber, {Yvonne G} and Roland Krause and Sanjay Sisodiya and Matthias Schwab and Thomas Sander and Holger Lerche",

year = "2020",

month = apr,

doi = "10.2217/pgs-2019-0179",

language = "English",

volume = "21",

pages = "325--335",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "5",

}

Wolking, S, Schulz, H, Nies, AT, McCormack, M, Schaeffeler, E, Auce, P, Avbersek, A, Becker, F, Klein, KM, Krenn, M, Møller, RS , Nikanorova, M, Weckhuysen, S, Consortium, EG, Cavalleri, GL, Delanty, N, Depondt, C, Johnson, MR, Koeleman, BP, Kunz, WS, Marson, AG, Sander, JW, Sills, GJ, Striano, P, Zara, F, Zimprich, F, Weber, YG, Krause, R, Sisodiya, S, Schwab, M, Sander, T & Lerche, H 2020, 'Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study', Pharmacogenomics, bind 21, nr. 5, s. 325-335. https://doi.org/10.2217/pgs-2019-0179

TY - JOUR

T1 - Pharmacoresponse in genetic generalized epilepsy

T2 - a genome-wide association study

AU - Wolking, Stefan

AU - Schulz, Herbert

AU - Nies, Anne T

AU - McCormack, Mark

AU - Schaeffeler, Elke

AU - Auce, Pauls

AU - Avbersek, Andreja

AU - Becker, Felicitas

AU - Klein, Karl M

AU - Krenn, Martin

AU - Møller, Rikke S

AU - Nikanorova, Marina

AU - Weckhuysen, Sarah

AU - Consortium, EpiPGx

AU - Cavalleri, Gianpiero L

AU - Delanty, Norman

AU - Depondt, Chantal

AU - Johnson, Michael R

AU - Koeleman, Bobby Pc

AU - Kunz, Wolfram S

AU - Marson, Anthony G

AU - Sander, Josemir W

AU - Sills, Graeme J

AU - Striano, Pasquale

AU - Zara, Federico

AU - Zimprich, Fritz

AU - Weber, Yvonne G

AU - Krause, Roland

AU - Sisodiya, Sanjay

AU - Schwab, Matthias

AU - Sander, Thomas

AU - Lerche, Holger

PY - 2020/4

Y1 - 2020/4

N2 - Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.

AB - Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE - responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.

U2 - 10.2217/pgs-2019-0179

DO - 10.2217/pgs-2019-0179

M3 - Article

C2 - 32308125

SN - 1462-2416

VL - 21

SP - 325

EP - 335

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 5

ER -

Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study

Abstract

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