A genome-wide association study in individuals of African ancestry reveals the importance of the Duffy-null genotype in the assessment of clozapine-related neutropenia.
Alleles
Antipsychotic Agents
/ therapeutic use
Black People
/ genetics
Clozapine
/ administration & dosage
Duffy Blood-Group System
/ genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
/ methods
Humans
Male
Neutropenia
/ blood
Neutrophils
/ drug effects
Polymorphism, Single Nucleotide
Receptors, Cell Surface
/ genetics
Risk Factors
Schizophrenia
/ genetics
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
30
07
2018
accepted:
26
11
2018
revised:
13
09
2018
pubmed:
17
1
2019
medline:
4
12
2019
entrez:
17
1
2019
Statut:
ppublish
Résumé
Individuals of African ancestry in the United States and Europe are at increased risk of developing schizophrenia and have poorer clinical outcomes. The antipsychotic clozapine, the only licensed medication for treatment-resistant schizophrenia, is under-prescribed and has high rates of discontinuation in individuals of African ancestry, due in part to increased rates of neutropenia. The genetic basis of lower neutrophil levels in those of African ancestry has not previously been investigated in the context of clozapine treatment. We sought to identify risk alleles in the first genome-wide association study of neutrophil levels during clozapine treatment, in 552 individuals with treatment-resistant schizophrenia and robustly inferred African genetic ancestry. Two genome-wide significant loci were associated with low neutrophil counts during clozapine treatment. The most significantly associated locus was driven by rs2814778 (β = -0.9, P = 4.21 × 10
Identifiants
pubmed: 30647433
doi: 10.1038/s41380-018-0335-7
pii: 10.1038/s41380-018-0335-7
doi:
Substances chimiques
ACKR1 protein, human
0
Antipsychotic Agents
0
Duffy Blood-Group System
0
Receptors, Cell Surface
0
Clozapine
J60AR2IKIC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
328-337Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : G0800509
Pays : International
Organisme : EC | Seventh Framework Programme (EC Seventh Framework Programme)
ID : 279227
Pays : International
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800509
Pays : United Kingdom
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/L011794/1
Pays : International
Organisme : Medical Research Council
ID : MR/L011794/1
Pays : United Kingdom
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