Evidence map›Paper›PMID 29160301›Full record

SynthesisThe pharmacogenomics journal2018

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

C Fabbri, K E Tansey, R H Perlis, J Hauser, N Henigsberg, W Maier, O Mors, A Placentino, M Rietschel, D Souery and 18 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The pharmacogenomics journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 4 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

26 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Precision Medicine in Antidepressants Treatment.Handbook of experimental pharmacology · 2023
    Review
  14. Article
  15. Identifying the Common Genetic Basis of Antidepressant Response.Biological psychiatry global open science · 2022
    Article
  16. Precision medicine in mood disorders.PCN reports : psychiatry and clinical neurosciences · 2022
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

28 authors.

C FabbriDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
K E TanseyCollege of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
R H PerlisDepartment of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA.
J HauserLaboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
N HenigsbergCroatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia.ORCID 0000-0002-5303-1834
W MaierDepartment of Psychiatry, University of Bonn, Bonn, Germany.
O MorsCentre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
A PlacentinoBiological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
M RietschelDivision of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
D SoueryLaboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel-Centre Européen de Psychologie Médicale, Brussels, Belgium.
G BreenInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2053-1792
C CurtisInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
L Sang-HyukInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
S NewhouseInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
H PatelInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
M GuipponiDepartment of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Geneva, Switzerland.
N PerroudDepartment of Psychiatry, University of Geneva, Geneva, Switzerland.
G BondolfiDepartment of Psychiatry, University of Geneva, Geneva, Switzerland.
M O'DonovanMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
G LewisDivision of Psychiatry, University College London (UCL), London, UK.
J M BiernackaDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
R M WeinshilboumDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
A FarmerInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
K J AitchisonDepartment of Psychiatry, University of Alberta, Edmonton, AB, Canada.
I CraigInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
P McGuffinInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
R UherDepartment of Psychiatry, Dalhousie University, Halifax, Canada.
C M LewisInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Funding

Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
INHERITED VARIATIONS IN DRUG-METABOLIZING ENZYMESR01GM028157 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 1985 to 2019
$6.9M
The Mayo Clinic Center for Individualized Treatment of Alcohol DependenceP20AA017830 · NIAAA · MAYO CLINIC ROCHESTER · PI CHOI, DOO-SUP · 2009 to 2010
$2.5M
Pharmacogenomics of Breast Cancer Adjuvant ChemotherapyU01HG005137 · NHGRI · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2009 to 2011
$2.1M
Pharmacogenomics and Mechanisms of Cytidine AnaloguesR01CA138461 · NCI · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI · 2009 to 2013
$1.5M
TREATMENT RESISTANT DEPRESSION-278990003N01MH090003 · NIMH · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · 1999 to 2003
–
Medical Research Council G0200243Medical Research Council G0701420NCI NIH HHS R01 CA138461NHGRI NIH HHS U01 HG005137NIAAA NIH HHS P20 AA017830NIGMS NIH HHS R01 GM028157NIGMS NIH HHS U19 GM061388NIMH NIH HHS N01 MH090003
6 · The paper itself

Abstract

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

Indexed as

Genome-Wide Association StudyAntidepressive AgentsGenetic VariationGenotypeHumansIntegrinsMajor Depressive DisorderNerve Tissue ProteinsPharmacogeneticsPolymorphism, Single NucleotideTreatment OutcomeAntidepressive AgentsIntegrinsITGA9 protein, humanNerve Tissue Proteinsneurexin IIIalpha

Identifiers

PMID29160301
PMCPMC10204124

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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.