Genetic associations with clozapine-induced myocarditis in patients with schizophrenia.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
27 01 2020
Historique:
received: 03 06 2019
accepted: 30 12 2019
revised: 09 12 2019
entrez: 19 2 2020
pubmed: 19 2 2020
medline: 22 6 2021
Statut: epublish

Résumé

Clozapine is the most effective antipsychotic drug for schizophrenia, yet it can cause life-threatening adverse drug reactions, including myocarditis. The aim of this study was to determine whether schizophrenia patients with clozapine-induced myocarditis have a genetic predisposition compared with clozapine-tolerant controls. We measured different types of genetic variation, including genome-wide single-nucleotide polymorphisms (SNPs), coding variants that alter protein expression, and variable forms of human leucocyte antigen (HLA) genes, alongside traditional clinical risk factors in 42 cases and 67 controls. We calculated a polygenic risk score (PRS) based on variation at 96 different genetic sites, to estimate the genetic liability to clozapine-induced myocarditis. Our genome-wide association analysis identified four SNPs suggestive of increased myocarditis risk (P < 1 × 10

Identifiants

pubmed: 32066683
doi: 10.1038/s41398-020-0722-0
pii: 10.1038/s41398-020-0722-0
pmc: PMC7026069
doi:

Substances chimiques

Antipsychotic Agents 0
Clozapine J60AR2IKIC

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

37

Subventions

Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom

Références

J Clin Psychiatry. 2012 Feb;73(2):252-4
pubmed: 22401481
Adv Pharmacol. 2018;83:155-190
pubmed: 29801574
AIDS. 1999 Jul 30;13(11):1419-20
pubmed: 10449301
Genomics Insights. 2017 Aug 01;10:1178631017721178
pubmed: 28811740
Pharmacogenomics J. 2017 Jul;17(4):304-311
pubmed: 28418011
Behav Brain Res. 2001 Nov 1;125(1-2):279-84
pubmed: 11682119
Exp Mol Pathol. 2017 Oct;103(2):137-140
pubmed: 28818508
Br J Psychiatry Suppl. 1992 May;(17):38-40
pubmed: 1418887
Circ Cardiovasc Genet. 2010 Jun;3(3):256-66
pubmed: 20445134
Nat Chem Biol. 2011 Aug 28;7(10):740-7
pubmed: 21873996
J Immunol. 2005 Jun 1;174(11):7085-95
pubmed: 15905552
Aust N Z J Psychiatry. 2011 Jun;45(6):458-65
pubmed: 21524186
J Biol Chem. 1997 Aug 1;272(31):19125-32
pubmed: 9235901
Aust N Z J Psychiatry. 2012 Sep;46(9):910-1
pubmed: 22956573
Nature. 2004 Apr 1;428(6982):486
pubmed: 15057820
N Engl J Med. 2008 Feb 7;358(6):568-79
pubmed: 18256392
Bioinformatics. 2015 May 1;31(9):1466-8
pubmed: 25550326
Schizophr Res. 2012 Nov;141(2-3):173-8
pubmed: 23010488
Pharmacogenetics. 2001 Mar;11(2):135-41
pubmed: 11266078
Schizophr Res. 2012 Feb;134(2-3):180-6
pubmed: 22113154
Acta Psychiatr Scand. 2015 Oct;132(4):231-40
pubmed: 25865238
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
CNS Drugs. 2019 Jan;33(1):81-91
pubmed: 30456745
J Clin Psychiatry. 2010 Aug;71(8):976-81
pubmed: 20361910
Mol Psychiatry. 2017 Oct;22(10):1509
pubmed: 27502474
PLoS Med. 2011 Sep;8(9):e1001092
pubmed: 21931540
Lancet. 2013 Sep 14;382(9896):951-62
pubmed: 23810019
Pharmacogenomics. 2006 Sep;7(6):813-8
pubmed: 16981842
Am J Med Genet A. 2013 Dec;161A(12):2953-63
pubmed: 24123848
Nucleic Acids Res. 2015 Jan;43(Database issue):D784-8
pubmed: 25414323
J Mol Endocrinol. 2010 May;44(5):259-69
pubmed: 20150327
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
BMC Immunol. 2008 Jan 22;9:1
pubmed: 18211710
Am J Psychiatry. 2016 Feb 1;173(2):166-73
pubmed: 26541815

Auteurs

Paul Lacaze (P)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. paul.lacaze@monash.edu.

Kathlyn J Ronaldson (KJ)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Eunice J Zhang (EJ)

MRC Centre for Drug Safety Science, Wolfson Centre for Personalised Medicine, University of Liverpool, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, and Liverpool Health Partners, Liverpool, UK.

Ana Alfirevic (A)

MRC Centre for Drug Safety Science, Wolfson Centre for Personalised Medicine, University of Liverpool, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, and Liverpool Health Partners, Liverpool, UK.

Hardik Shah (H)

Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Leah Newman (L)

Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Maya Strahl (M)

Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Melissa Smith (M)

Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Chad Bousman (C)

Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada.

Ben Francis (B)

Department of Biostatistics, University of Liverpool, Liverpool, UK.

Andrew P Morris (AP)

Department of Biostatistics, University of Liverpool, Liverpool, UK.
Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.

Trevor Wilson (T)

Medical Genomics Facility, Hudson Institute of Medical Research, Melbourne, VIC, Australia.

Fernando Rossello (F)

University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

David Powell (D)

Bioinformatics Platform, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.

Vivien Vasic (V)

Medical Genomics Facility, Hudson Institute of Medical Research, Melbourne, VIC, Australia.

Robert Sebra (R)

Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

John J McNeil (JJ)

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Munir Pirmohamed (M)

MRC Centre for Drug Safety Science, Wolfson Centre for Personalised Medicine, University of Liverpool, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, and Liverpool Health Partners, Liverpool, UK.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH