PMID- 25768306
OWN - NLM
STAT- MEDLINE
DCOM- 20160317
LR  - 20201217
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - A naturally occurring null variant of the NMDA type glutamate receptor NR3B 
      subunit is a risk factor of schizophrenia.
PG  - e0116319
LID - 10.1371/journal.pone.0116319 [doi]
LID - e0116319
AB  - Hypofunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been 
      implicated in the pathogenesis of schizophrenia. Here, we investigated the 
      significance of a common human genetic variation of the NMDAR NR3B subunit that 
      inserts 4 bases within the coding region (insCGTT) in the pathogenesis of 
      schizophrenia. The cDNA carrying this polymorphism generates a truncated protein, 
      which is electrophysiologically non-functional in heterologous expression 
      systems. Among 586 schizophrenia patients and 754 healthy controls, insCGTT was 
      significantly overrepresented in patients compared to controls (odds ratio = 
      1.37, p = 0.035). Among 121 schizophrenia patients and 372 healthy controls, 
      genetic analyses of normal individuals revealed that those carrying insCGTT have 
      a predisposition to schizotypal personality traits (F1,356 = 4.69, p = 0.031). 
      Furthermore, pre-pulse inhibition, a neurobiological trait disturbed in patients 
      with schizophrenia, was significantly impaired in patients carrying insCGTT 
      compared with those with the major allele (F1,116 = 5.72, p = 0.018, F1,238 = 
      4.46, p = 0.036, respectively). These results indicate that a naturally occurring 
      null variant in NR3B could be a risk factor of schizophrenia.
FAU - Matsuno, Hitomi
AU  - Matsuno H
AD  - Brain Science Institute, RIKEN, Wako, Saitama, 351-0198, Japan.
FAU - Ohi, Kazutaka
AU  - Ohi K
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan.
FAU - Hashimoto, Ryota
AU  - Hashimoto R
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan; Molecular Research Center for Children's Mental Development, 
      United Graduate School of Child Development, Osaka University, Osaka, 565-0871, 
      Japan.
FAU - Yamamori, Hidenaga
AU  - Yamamori H
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan; Department of Molecular Neuropsychiatry, Osaka University 
      Graduate School of Medicine, Osaka, 565-0871, Japan.
FAU - Yasuda, Yuka
AU  - Yasuda Y
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan.
FAU - Fujimoto, Michiko
AU  - Fujimoto M
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan.
FAU - Yano-Umeda, Satomi
AU  - Yano-Umeda S
AD  - Department of Molecular Neuropsychiatry, Osaka University Graduate School of 
      Medicine, Osaka, 565-0871, Japan.
FAU - Saneyoshi, Takeo
AU  - Saneyoshi T
AD  - Brain Science Institute, RIKEN, Wako, Saitama, 351-0198, Japan.
FAU - Takeda, Masatoshi
AU  - Takeda M
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, 
      565-0871, Japan.
FAU - Hayashi, Yasunori
AU  - Hayashi Y
AD  - Brain Science Institute, RIKEN, Wako, Saitama, 351-0198, Japan; Saitama 
      University Brain Science Institute, Saitama University, Saitama, 338-8570, Japan.
LA  - eng
GR  - R21 NS046421/NS/NINDS NIH HHS/United States
GR  - R21NS46421/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150313
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (NR3B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, N-Methyl-D-Aspartate/*genetics
MH  - Schizophrenia/*genetics/pathology
PMC - PMC4358936
COIS- Competing Interests: The authors have read the journal's policy and have the 
      following competing interests: Y.H. is partly supported by Takeda Pharmaceuticals 
      Co. Ltd. and Fujitsu Laboratories. This does not alter the authors' adherence to 
      PLOS ONE policies on sharing data and materials.
EDAT- 2015/03/15 06:00
MHDA- 2016/03/18 06:00
PMCR- 2015/03/13
CRDT- 2015/03/14 06:00
PHST- 2014/05/22 00:00 [received]
PHST- 2014/12/08 00:00 [accepted]
PHST- 2015/03/14 06:00 [entrez]
PHST- 2015/03/15 06:00 [pubmed]
PHST- 2016/03/18 06:00 [medline]
PHST- 2015/03/13 00:00 [pmc-release]
AID - PONE-D-14-22962 [pii]
AID - 10.1371/journal.pone.0116319 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 13;10(3):e0116319. doi: 10.1371/journal.pone.0116319. 
      eCollection 2015.