Evidence map›Paper›PMID 25666758›Full record

ArticleMolecular psychiatry2015

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

J J Luykx, S C Bakker, W F Visser, N Verhoeven-Duif, J E Buizer-Voskamp, J M den Heijer, M P M Boks, J H Sul, E Eskin, A P Ori and 12 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders.The international journal of neuropsychopharmacology · 2015
    Review
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

22 authors at 6 institutions in 3 countries.

J J LuykxHuman Neurogenetics Unit, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
S C BakkerDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
W F VisserDepartment of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
N Verhoeven-DuifDepartment of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
J E Buizer-VoskampDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
J M den HeijerDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
M P M BoksDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
J H SulComputer Science Department, University of California, Los Angeles, CA, USA.
E EskinComputer Science Department, University of California, Los Angeles, CA, USA.
A P OriCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
R M CantorDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
J VorstmanDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
E StrengmanDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
J DeYoungCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
T H KappenDepartment of Anesthesiology, Intensive Care and Pain Management, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
E PariamaDepartment of Anesthesiology, Intensive Care and Pain Management, Diakonessenhuis Hospital, Utrecht, The Netherlands.
E P A van DongenDepartment of Anesthesiology, Intensive Care & Pain Management, St Antonius Hospital, Nieuwegein, The Netherlands.
P BorgdorffDepartment of Anesthesiology, Intensive Care and Pain Management, Diakonessenhuis Hospital, Utrecht, The Netherlands.
P BruinsDepartment of Anesthesiology, Intensive Care & Pain Management, St Antonius Hospital, Nieuwegein, The Netherlands.
T J de KoningDepartment of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
R S KahnDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
R A OphoffDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
University Medical Center Utrecht · NLUniversity of California, Los Angeles · USDiakonessenhuis hospital · NLSt. Antonius Ziekenhuis · NLWilhelmina Children's Hospital · NLZiekenhuisnetwerk Antwerpen Stuivenberg · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (β=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (β=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

Indexed as

AdolescentAdultAlanineChromatography, LiquidFemaleGenetic VariationGenome-Wide Association StudyGlycineHumansMaleMembrane Transport ProteinsMiddle AgedProlineProline OxidaseQuantitative Trait LociReceptors, N-Methyl-D-AspartateAlanineGlycineMembrane Transport ProteinsPRODH protein, humanProlineProline OxidaseReceptors, N-Methyl-D-AspartateSerineSLC6A20 protein, human

Identifiers

PMID25666758
OpenAlexW1968299778

What OpenQuestion holds

Textmetadata
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.