Evidence map›Paper›PMID 27400856›Full record

SynthesisMolecular psychiatry2017

Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia.

S E Legge, M L Hamshere, S Ripke, A F Pardinas, J I Goldstein, E Rees, A L Richards, G Leonenko, L F Jorskog, Clozapine-Induced Agranulocytosis Consortium and 19 more

Erratum issuedOpen access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
10.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Rare variants in pharmacogenes influence clozapine metabolism in individuals with schizophrenia.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2024
    Article
  14. The time is now to start evaluating biomarkers in the clinic.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2023
    Article
  15. Review
  16. Article
  17. Article
  18. Reduction in Absolute Neutrophil Counts in Patient on Clozapine Infected with COVID-19.International journal of environmental research and public health · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 6 institutions in 5 countries.

S E LeggeMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
M L HamshereMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
S RipkeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-3622-835X
A F PardinasMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
J I GoldsteinAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
E ReesMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
A L RichardsMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
G LeonenkoMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
L F JorskogDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Clozapine-Induced Agranulocytosis Consortium
K D ChambertAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
D A CollierKing's College London, SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, Denmark Hill, London, UK.
G GenoveseStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
I GieglingDepartment of Psychiatry, University of Halle, Halle, Germany.
P HolmansMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
A JonasdottirdeCODE genetics, Sturlugata 8, Reykjavik, Iceland.
G KirovMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
S A McCarrollStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
J H MacCabeKing's College London, Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, London, USA.
K MantripragadaMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
J L MoranStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
B M NealeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
H StefanssondeCODE genetics, Sturlugata 8, Reykjavik, Iceland.
D RujescuDepartment of Psychiatry, University of Halle, Halle, Germany.
M J DalyAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
P F SullivanDepartment of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
M J OwenMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
M C O'DonovanMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
J T R WaltersMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Cardiff University · GBBroad Institute · USdeCODE Genetics (Iceland) · ISKing's College London · GBUniversity of North Carolina at Chapel Hill · USLudwig-Maximilians-Universität München · DE

Funding

Medical Research Council G0800509Medical Research Council MR/L010305/1Medical Research Council MR/P005748/1
6 · The paper itself

Abstract

The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10

Indexed as

Carrier ProteinsCase-Control StudiesClozapineExomeFemaleGenome-Wide Association StudyHLA-DQ beta-ChainsHumansMaleNeutropeniaOdds RatioSchizophreniaSolute Carrier Organic Anion Transporter Family Member 1B3Carrier ProteinsClozapineHLA-DQB1 antigenHLA-DQ beta-ChainsSolute Carrier Organic Anion Transporter Family Member 1B3STARD9 protein, human

Identifiers

PMID27400856
PMCPMC5065090
OpenAlexW2472691387

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.