Evidence map›Paper›PMID 23319000›Full record

ArticleMolecular psychiatry2014

Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

J J Luykx, S C Bakker, E Lentjes, M Neeleman, E Strengman, L Mentink, J DeYoung, S de Jong, J H Sul, E Eskin and 14 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
4.4field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.

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  20. ThePharmacogenomics · 2019
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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

24 authors at 7 institutions in 2 countries.

J J Luykx1] Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
S C BakkerDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
E LentjesDepartment of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
M NeelemanDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
E StrengmanDepartment of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
L Mentink1] Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
J DeYoungCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
S de JongCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
J H SulComputer Science Department, University of California, Los Angeles, Los Angeles, CA, USA.
E Eskin1] Computer Science Department, University of California, Los Angeles, Los Angeles, CA, USA [2] Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
K van EijkDepartment of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
J van SettenDepartment of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
J E Buizer-VoskampDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
R M CantorDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
A LuDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
M van AmerongenDepartment of Anesthesiology, Ter Gooi Hospitals, Hilversum, The Netherlands.
E P A van DongenDepartment of Anesthesiology, Intensive Care and Pain Management, St Antonius Hospital, Nieuwegein, The Netherlands.
P KeijzersDepartment of Anesthesiology, Central Military Hospital, Utrecht, The Netherlands.
T KappenDepartment of Anesthesiology, Intensive Care and Pain Management, University Medical Center Utrecht, Utrecht, The Netherlands.
P BorgdorffDepartment of Anesthesiology, Intensive Care and Pain Management, Diakonessenhuis Hospital, Utrecht, The Netherlands.
P BruinsDepartment of Anesthesiology, Intensive Care and Pain Management, St Antonius Hospital, Nieuwegein, The Netherlands.
E M DerksAcademic Medical Center, Department of Psychiatry, Amsterdam, The Netherlands.
R S KahnDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
R A Ophoff1] Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands [2] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA [3] Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
University Medical Center Utrecht · NLUniversity of California, Los Angeles · USSt. Antonius Ziekenhuis · NLAcademic Medical Center · NLCentral Military Hospital · NLDiakonessenhuis hospital · NLTergooi · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized β=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (β=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes.

Indexed as

Gene ExpressionGenome-Wide Association Study3',5'-Cyclic-AMP PhosphodiesterasesAdultBiogenic MonoaminesChromosomes, Human, Pair 11FemaleGenetic LociGenetic VariationGenotyping TechniquesHomovanillic AcidHumansHydroxyindoleacetic AcidLinear ModelsMaleMembrane Proteins3',5'-Cyclic-AMP PhosphodiesterasesBiogenic MonoaminesCSMD1 protein, humanHomovanillic AcidHydroxyindoleacetic AcidMembrane ProteinsMethoxyhydroxyphenylglycolPDE9A protein, humanTumor Suppressor Proteins

Identifiers

PMID23319000
OpenAlexW2095305985

What OpenQuestion holds

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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.