Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders.
PSD-95 associated PSD proteins play a critical role in regulating the density and activity of glutamate receptors. Numerous previous studies have shown an association between the genes that encode these proteins and schizophrenia (SZ) and autism spectrum disorders (ASD), which share a substantial portion of genetic risks. We sequenced the protein-encoding regions of DLG1, DLG2, DLG4, DLGAP1, DLGAP2, and SynGAP in 562 cases (370 SZ and 192 ASD patients) on the Ion PGM platform. We detected 26 rare (minor allele frequency <1%), non-synonymous mutations, and conducted silico functional analysis and pedigree analysis when possible. Three variants, G344R in DLG1, G241S in DLG4, and R604C in DLGAP2, were selected for association analysis in an independent sample set of 1315 SZ patients, 382 ASD patients, and 1793 healthy controls. Neither DLG4-G241S nor DLGAP2-R604C was detected in any samples in case or control sets, whereas one additional SZ patient was found that carried DLG1-G344R. Our results suggest that rare missense mutations in the candidate PSD genes may increase susceptibility to SZ and/or ASD. These findings may strengthen the theory that rare, non-synonymous variants confer substantial genetic risks for these disorders.
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Jingrui
J
Xing
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Hiroki
H
Kimura
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Chenyao
C
Wang
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Kanako
K
Ishizuka
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.|Institute for Advanced Research, Nagoya University, 466-8550 Nagoya, Japan.
Itaru
I
Kushima
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Yuko
Y
Arioka
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Akira
A
Yoshimi
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Yukako
Y
Nakamura
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Tomoko
T
Shiino
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Tomoko
T
Oya-Ito
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Yuto
Y
Takasaki
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Yota
Y
Uno
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Takashi
T
Okada
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Tetsuya
T
Iidaka
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Branko
B
Aleksic
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Daisuke
D
Mori
Department of Psychiatry, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan.
Norio
N
Ozaki
D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D000076122:Disks Large Homolog 4 Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012559:Schizophrenia / Q000235:genetics*
D000076122:Disks Large Homolog 4 Protein