Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study-Reference-Cited by-同舟云学术

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

Published:2020-04 Issue:5 Volume:21 Page:325-335
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Wolking Stefan¹²^ORCID,Schulz Herbert³,Nies Anne T⁴⁵,McCormack Mark⁶,Schaeffeler Elke⁴⁵,Auce Pauls⁷,Avbersek Andreja⁸,Becker Felicitas¹,Klein Karl M⁹,Krenn Martin¹⁰,Møller Rikke S¹¹¹²,Nikanorova Marina¹¹,Weckhuysen Sarah¹³¹⁴¹⁵,Consortium EpiPGx,Cavalleri Gianpiero L⁶¹⁶,Delanty Norman⁶¹⁷¹⁸,Depondt Chantal¹⁹,Johnson Michael R¹⁶,Koeleman Bobby PC²⁰,Kunz Wolfram S²¹,Marson Anthony G²²,Sander Josemir W⁸²³,Sills Graeme J²²,Striano Pasquale²⁴²⁵,Zara Federico²⁶,Zimprich Fritz¹⁰,Weber Yvonne G¹,Krause Roland²⁷^ORCID,Sisodiya Sanjay⁸,Schwab Matthias⁴²⁸²⁹,Sander Thomas³,Lerche Holger¹

Affiliation:

1. Department of Neurology & Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany

2. Department of Neurosciences, CHUM Research Center, University of Montreal, Montreal, H2X 0A9, Canada

3. Cologne Center for Genomics, University of Cologne, 50931 Cologne, Germany

4. Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany

5. University of Tübingen, 72076 Tübingen, Germany

6. Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland

7. Walton Centre NHS Foundation Trust, Liverpool, L33 4YD, UK

8. Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, London & Chalfont Centre for Epilepsy, London, SL9 0RJ, UK

9. Epilepsy Center Frankfurt Rhine-Main, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt, Germany

10. Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria

11. Danish Epilepsy Centre – Filadelfia, 4293 Dianalund, Denmark

12. Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark

13. Neurogenetics Group, Center for Molecular Neurology, VIB-University of Antwerp, 2650 Edegem, Belgium

14. Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, 2650 Edegem, Belgium

15. Department of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium

16. Division of Brain Sciences, Imperial College Faculty of Medicine, London, SW2 2AZ, UK

17. Division of Neurology, Beaumont Hospital, Dublin 9, Ireland

18. The FutureNeuro Research Centre, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland

19. Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium

20. Department of Genetics, University Medical Center Utrecht, 3584 Utrecht, The Netherlands

21. Institute of Experimental Epileptology & Cognition Research & Department of Epileptology, University of Bonn, 53127 Bonn, Germany

22. Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 7ZB, UK

23. Stichting Epilepsie Instellingen Nederland (SEIN), 2103 Heemstede, The Netherlands

24. Pediatric Neurology & Muscular Diseases Unit, IRCCS ‘G. Gaslini’ Institute, 16147 Genova, Italy

25. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal & Child Health, University of Genova, 16147 Genova, Italy

26. Laboratory of Neurogenetics and Neuroscience, IRCCS ‘G. Gaslini’ Institute, 16147 Genova, Italy

27. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg

28. Department of Clinical Pharmacology, University Hospital Tübingen, 72076 Tübingen, Germany

29. Department of Pharmacy & Biochemistry, University Tübingen, 72076 Tübingen, Germany

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2019-0179

Reference61 articles.

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