Evidence map›Paper›PMID 19721433›Full record

Trial reportMolecular psychiatry2011

Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics.

J L McClay, D E Adkins, K Aberg, S Stroup, D O Perkins, V I Vladimirov, J A Lieberman, P F Sullivan, E J C G van den Oord

Abstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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

74 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
  2. Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019
    Pooled it
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  5. Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2015
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

J L McClayCenter for Biomarker Research and Personalized Medicine, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA. jlmcclay@vcu.edu
D E Adkins
K Aberg
S Stroup
D O Perkins
V I Vladimirov
J A Lieberman
P F Sullivan
E J C G van den Oord

Funding

PUBLIC EDUCATION CAMPAIGN ON DEPRESSION DARTN01MH090001 · NIMH · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · 1989 to 2003
$10.4M
A Large-Scale Schizophrenia Association Study in SwedenR01MH077139 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2007 to 2018
$9.9M
Design and analysis of adaptive multistage genetic association studiesR01HG004240 · NHGRI · VIRGINIA COMMONWEALTH UNIVERSITY · PI VAN DEN OORD, EDWIN · 2008 to 2010
$1.0M
A genome-wide association study to detect genetic variation for schizophreniaR01MH078069 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI VAN DEN OORD, EDWIN · 2008 to 2010
$905k
Replication of Schizophrenia Associations in CATIER01MH074027 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2006 to 2007
$715k
NHGRI NIH HHS R01 HG004240NIMH NIH HHS N01 MH090001NIMH NIH HHS R01 MH074027NIMH NIH HHS R01 MH077139NIMH NIH HHS R01 MH078069
6 · The paper itself

Abstract

Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenia patients to the most effective and safe medication. In this study, we use a genome-wide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness. Subjects were genotyped using the Affymetrix 500 K genotyping platform plus a custom 164 K chip to improve genome-wide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale. Our criterion for genome-wide significance was a prespecified threshold that ensures that, on an average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our prespecified threshold and involved a single-nucleotide polymorphism (SNP) in an intergenic region on chromosome 4p15. In addition, SNPs in Ankyrin Repeat and Sterile Alpha Motif Domain-Containing Protein 1B (ANKS1B) and in the Contactin-Associated Protein-Like 5 gene (CNTNAP5), which mediated the effects of olanzapine and risperidone on Negative symptoms, were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino-acid substitution. In addition to highlighting our top results, we provide all P-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of genome-wide association studies to discover novel genes that mediate the effects of antipsychotics, which could eventually help to tailor drug treatment to schizophrenic patients.

Indexed as

Chromosomes, Human, Pair 4PharmacogeneticsAntipsychotic AgentsBenzodiazepinesDibenzothiazepinesDouble-Blind MethodFollow-Up StudiesGenome-Wide Association StudyHumansOlanzapinePerphenazinePiperazinesPolymorphism, Single NucleotideQuetiapine FumarateRisperidoneSchizophreniaAntipsychotic AgentsBenzodiazepinesDibenzothiazepinesOlanzapinePerphenazinePiperazinesQuetiapine FumarateRisperidoneThiazolesziprasidone

Identifiers

PMID19721433
PMCPMC2888895

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.