PMID- 25666758
OWN - NLM
STAT- MEDLINE
DCOM- 20160829
LR  - 20181113
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Linking)
VI  - 20
IP  - 12
DP  - 2015 Dec
TI  - Genome-wide association study of NMDA receptor coagonists in human cerebrospinal 
      fluid and plasma.
PG  - 1557-64
LID - 10.1038/mp.2014.190 [doi]
AB  - 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 
      (beta=0.29; P=6.38 x 10(-10)). The missense variant rs17279437 in the proline 
      transporter SLC6A20 was associated with L-proline in CSF (beta=0.28; P=9.68 x 
      10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF 
      ratio at the D-amino-acid oxidase (DAO) gene (beta=-0.28; P=9.08 x 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.
FAU - Luykx, J J
AU  - Luykx JJ
AD  - Human Neurogenetics Unit, Brain Center Rudolf Magnus, University Medical Center 
      Utrecht (UMCU), Utrecht, The Netherlands.
AD  - Department of Psychiatry, ZNA Hospitals, Antwerp, Belgium.
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Bakker, S C
AU  - Bakker SC
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Visser, W F
AU  - Visser WF
AD  - Department of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina 
      Children's Hospital, Utrecht, The Netherlands.
FAU - Verhoeven-Duif, N
AU  - Verhoeven-Duif N
AD  - Department of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina 
      Children's Hospital, Utrecht, The Netherlands.
FAU - Buizer-Voskamp, J E
AU  - Buizer-Voskamp JE
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - den Heijer, J M
AU  - den Heijer JM
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Boks, M P M
AU  - Boks MP
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Sul, J H
AU  - Sul JH
AD  - Computer Science Department, University of California, Los Angeles, CA, USA.
FAU - Eskin, E
AU  - Eskin E
AD  - Computer Science Department, University of California, Los Angeles, CA, USA.
AD  - Department of Human Genetics, University of California, Los Angeles, CA, USA.
FAU - Ori, A P
AU  - Ori AP
AD  - Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human 
      Behavior, University of California Los Angeles, Los Angeles, CA, USA.
FAU - Cantor, R M
AU  - Cantor RM
AD  - Department of Human Genetics, University of California, Los Angeles, CA, USA.
FAU - Vorstman, J
AU  - Vorstman J
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Strengman, E
AU  - Strengman E
AD  - Department of Human Genetics, University of California, Los Angeles, CA, USA.
FAU - DeYoung, J
AU  - DeYoung J
AD  - Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human 
      Behavior, University of California Los Angeles, Los Angeles, CA, USA.
FAU - Kappen, T H
AU  - Kappen TH
AD  - Department of Anesthesiology, Intensive Care and Pain Management, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Pariama, E
AU  - Pariama E
AD  - Department of Anesthesiology, Intensive Care and Pain Management, Diakonessenhuis 
      Hospital, Utrecht, The Netherlands.
FAU - van Dongen, E P A
AU  - van Dongen EP
AD  - Department of Anesthesiology, Intensive Care & Pain Management, St Antonius 
      Hospital, Nieuwegein, The Netherlands.
FAU - Borgdorff, P
AU  - Borgdorff P
AD  - Department of Anesthesiology, Intensive Care and Pain Management, Diakonessenhuis 
      Hospital, Utrecht, The Netherlands.
FAU - Bruins, P
AU  - Bruins P
AD  - Department of Anesthesiology, Intensive Care & Pain Management, St Antonius 
      Hospital, Nieuwegein, The Netherlands.
FAU - de Koning, T J
AU  - de Koning TJ
AD  - Department of Metabolic Diseases, University Medical Center Utrecht/Wilhelmina 
      Children's Hospital, Utrecht, The Netherlands.
AD  - University of Groningen, University Medical Center Groningen, Department of 
      Genetics, Groningen, The Netherlands.
FAU - Kahn, R S
AU  - Kahn RS
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
FAU - Ophoff, R A
AU  - Ophoff RA
AD  - Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University 
      Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
AD  - Department of Human Genetics, University of California, Los Angeles, CA, USA.
AD  - Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human 
      Behavior, University of California Los Angeles, Los Angeles, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20150210
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (SLC6A20 protein, human)
RN  - 452VLY9402 (Serine)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.5.3.- (Proline Oxidase)
RN  - EC 1.5.5.2 (PRODH protein, human)
RN  - OF5P57N2ZX (Alanine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alanine/blood/cerebrospinal fluid/*metabolism
MH  - Chromatography, Liquid
MH  - Female
MH  - Genetic Variation
MH  - Genome-Wide Association Study
MH  - Glycine/blood/cerebrospinal fluid/*metabolism
MH  - Humans
MH  - Male
MH  - Membrane Transport Proteins/genetics
MH  - Middle Aged
MH  - Proline/blood/cerebrospinal fluid/*metabolism
MH  - Proline Oxidase/genetics
MH  - Quantitative Trait Loci
MH  - Receptors, N-Methyl-D-Aspartate/*agonists
MH  - Serine/blood/cerebrospinal fluid/*metabolism
MH  - Tandem Mass Spectrometry
MH  - Young Adult
EDAT- 2015/02/11 06:00
MHDA- 2016/08/30 06:00
CRDT- 2015/02/11 06:00
PHST- 2014/09/18 00:00 [received]
PHST- 2014/11/05 00:00 [revised]
PHST- 2014/12/08 00:00 [accepted]
PHST- 2015/02/11 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2016/08/30 06:00 [medline]
AID - mp2014190 [pii]
AID - 10.1038/mp.2014.190 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2015 Dec;20(12):1557-64. doi: 10.1038/mp.2014.190. Epub 2015 Feb 
      10.