A pharmacogenomic assessment of psychiatric adverse drug reactions to levetiracetam.
adverse drug reactions
levetiracetam
pharmacogenomics
polygenic risk scoring
psychosis
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
14
03
2022
received:
17
01
2022
accepted:
14
03
2022
pubmed:
18
3
2022
medline:
7
6
2022
entrez:
17
3
2022
Statut:
ppublish
Résumé
Levetiracetam (LEV) is an effective antiseizure medicine, but 10%-20% of people treated with LEV report psychiatric side-effects, and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic variation to psychiatric and behavioral ADRs associated with LEV. This case-control study compared cases of LEV-associated behavioral disorder (n = 149) or psychotic reaction (n = 37) to LEV-exposed people with no history of psychiatric ADRs (n = 920). All samples were of European ancestry. We performed genome-wide association study (GWAS) analysis comparing those with LEV ADRs to controls. We estimated the polygenic risk scores (PRS) for schizophrenia and compared cases with LEV-associated psychotic reaction to controls. Rare variant burden analysis was performed using exome sequence data of cases with psychotic reactions (n = 18) and controls (n = 122). Univariate GWAS found no significant associations with either LEV-associated behavioural disorder or LEV-psychotic reaction. PRS analysis showed that cases of LEV-associated psychotic reaction had an increased PRS for schizophrenia relative to contr ols (p = .0097, estimate = .4886). The rare-variant analysis found no evidence of an increased burden of rare genetic variants in people who had experienced LEV-associated psychotic reaction relative to controls. The polygenic burden for schizophrenia is a risk factor for LEV-associated psychotic reaction. To assess the clinical utility of PRS as a predictor, it should be tested in an independent and ideally prospective cohort. Larger sample sizes are required for the identification of significant univariate common genetic signals or rare genetic signals associated with psychiatric LEV ADRs.
Identifiants
pubmed: 35298028
doi: 10.1111/epi.17228
pmc: PMC9321556
doi:
Substances chimiques
Anticonvulsants
0
Levetiracetam
44YRR34555
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1563-1570Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Epilepsia. 2013 Jan;54(1):36-44
pubmed: 22881836
Neurology. 2018 Jan 23;90(4):e332-e341
pubmed: 29288229
J Clin Psychiatry. 2004 Sep;65(9):1162-3
pubmed: 15367040
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Am J Hum Genet. 2017 Apr 6;100(4):635-649
pubmed: 28366442
Epilepsy Behav. 2017 Nov;76:24-31
pubmed: 28931473
Brain. 2016 Oct;139(Pt 10):2668-2678
pubmed: 27503872
Seizure. 2011 Sep;20(7):554-7
pubmed: 21531583
Seizure. 2012 Jul;21(6):466-70
pubmed: 22608976
Seizure. 2003 Apr;12(3):131-5
pubmed: 12651076
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Am J Hum Genet. 2012 Aug 10;91(2):224-37
pubmed: 22863193
Nat Genet. 2007 Jul;39(7):906-13
pubmed: 17572673
Nature. 2004 Apr 1;428(6982):486
pubmed: 15057820
Epilepsia. 2012 Jan;53(1):111-9
pubmed: 22050371
JAMA Psychiatry. 2018 Jan 1;75(1):65-74
pubmed: 29121268
N Engl J Med. 2011 Mar 24;364(12):1134-43
pubmed: 21428769
Nat Rev Genet. 2005 Apr;6(4):333-40
pubmed: 15803201
Epilepsia. 2022 Jun;63(6):1563-1570
pubmed: 35298028
Gigascience. 2019 Jul 1;8(7):
pubmed: 31307061
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Clin Transplant. 2020 Aug;34(8):e13904
pubmed: 32400091
Seizure. 2014 Mar;23(3):184-90
pubmed: 24315662
JAMA Neurol. 2018 Mar 1;75(3):279-286
pubmed: 29279892
Seizure. 2005 Jan;14(1):23-7
pubmed: 15642496
Expert Opin Drug Discov. 2007 Nov;2(11):1537-45
pubmed: 23484603
Hum Genomics. 2018 May 25;12(1):26
pubmed: 29793534
Trends Pharmacol Sci. 2004 Apr;25(4):193-200
pubmed: 15063083
Seizure. 2015 Sep;31:49-55
pubmed: 26362377
Neurology. 2007 Feb 6;68(6):402-8
pubmed: 17283312
JAMA Neurol. 2019 Apr 1;76(4):440-446
pubmed: 30688969
Genome Med. 2020 May 18;12(1):44
pubmed: 32423490
BMC Genet. 2008 May 13;9:36
pubmed: 18477402
Nat Neurosci. 2020 Feb;23(2):179-184
pubmed: 31932766
Pharmaceuticals (Basel). 2010 Jul 26;3(8):2362-2379
pubmed: 27713357
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Bioinformatics. 2016 May 1;32(9):1423-6
pubmed: 27153000
Ther Drug Monit. 2004 Oct;26(5):534-40
pubmed: 15385837
Genome Res. 2012 Jan;22(1):1-8
pubmed: 22147369
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Epilepsy Behav Rep. 2021 Aug 08;16:100474
pubmed: 34458714
Allergy. 2019 Nov;74(11):2227-2230
pubmed: 30972788