Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population.
N-methyl-d-aspartate receptors (NMDARs) play a critical role in excitatory synaptic transmission and plasticity in the central nervous systems. Recent genetics studies in schizophrenia (SCZ) show that SCZ is susceptible to NMDARs and the NMDAR signaling complex. In autism spectrum disorder (ASD), several studies report dysregulation of NMDARs as a risk factor for ASD. To further examine the association between NMDARs and SCZ/ASD development, we conducted a mutation screening study of GRIN2B which encodes NR2B subunit of NMDARs, to identify rare mutations that potentially cause diseases, in SCZ and ASD patients (n = 574 and 152, respectively). This was followed by an association study in a large sample set of SCZ, ASD, and normal healthy controls (n = 4145, 381, and 4432, respectively). We identified five rare missense mutations through the mutation screening of GRIN2B. Although no statistically significant association between any single mutation and SCZ or ASD was found, one of its variant, K1292R, is found only in the patient group. To further examine the association between mutations in GRIN2B and SCZ/ASD development, a larger sample size and functional experiments are needed.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Yuto
Y
Takasaki
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Takayoshi
T
Koide
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Chenyao
C
Wang
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Hiroki
H
Kimura
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Jingrui
J
Xing
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|Institute for Advanced Research, Nagoya University, Nagoya, Aichi, Japan.
Itaru
I
Kushima
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Kanako
K
Ishizuka
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|Brain and Mind Research Center, Nagoya University, Nagoya, Aichi, Japan.
Daisuke
D
Mori
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|Department of Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Mariko
M
Sekiguchi
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Masashi
M
Ikeda
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Miki
M
Aizawa
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Naoko
N
Tsurumaru
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Yoshimi
Y
Iwayama
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Akira
A
Yoshimi
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, Japan.
Yuko
Y
Arioka
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Mami
M
Yoshida
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Hiromi
H
Noma
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Tomoko
T
Oya-Ito
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Yukako
Y
Nakamura
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Shohko
S
Kunimoto
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Branko
B
Aleksic
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Yota
Y
Uno
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Takashi
T
Okada
Department of Psychiatry, Ujike Nishiguchi Clinic (HU), Okayama, Japan.
Hiroshi
H
Ujike
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Department of Pediatric Psychiatry, Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
Jun
J
Egawa
Department of Child Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hitoshi
H
Kuwabara
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Toshiyuki
T
Someya
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Takeo
T
Yoshikawa
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Nakao
N
Iwata
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Norio
N
Ozaki
D000293:Adolescent; D000328:Adult; D000368:Aged; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate