Association analysis of HSP90B1 with bipolar disorder.
Pathophysiological role of endoplasmic reticulum (ER) stress response signaling has been suggested for bipolar disorder. The goal of this study was to test the genetic association between bipolar disorder and an ER chaperone gene, HSP90B1 (GRP94/gp96), which is located on a candidate locus, 12q23.3. We tested the genetic association between bipolar disorder and HSP90B1 by case-control studies in two independent Japanese sample sets and by a transmission disequilibrium test (TDT) in NIMH Genetics initiative bipolar trio samples (NIMH trios). We also performed gene expression analysis of HSP90B1 in lymphoblastoid cells. Among the 11 SNPs tested, rs17034977 showed significant association in both Japanese sample sets. The frequency of the SNP was lower in NIMH samples than in Japanese samples and there was no significant association in NIMH trios. Gene expression analysis of HSP90B1 in lymphoblastoid cells suggested a possible relationship between the associated SNP and mRNA levels. HSP90B1 may have a pathophysiological role in bipolar disorder in the Japanese population, though further study will be needed to understand the underlying functional mechanisms.
Kakiuchi
Chihiro
C
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Ishiwata
Mizuho
M
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Nanko
Shinichiro
S
Department of Psychiatry and Genome Research Center, Teikyo University School of Medicine, Tokyo, Japan.
Kunugi
Hiroshi
H
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Minabe
Yoshio
Y
Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Nakamura
Kazuhiko
K
Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mori
Norio
N
Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Fujii
Kumiko
K
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
Umekage
Tadashi
T
Department of Psychiatry, Health Service Center, University of Tokyo, Tokyo, Japan.
Tochigi
Mamoru
M
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.|Department of Neuropsychiatry, Faculty of Medicine, University of Tokyo, Bunkyo, Tokyo, Japan.
Kohda
Kazuhisa
K
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Sasaki
Tsukasa
T
Department of Psychiatry, Health Service Center, University of Tokyo, Tokyo, Japan.
Yamada
Kazuo
K
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
Yoshikawa
Takeo
T
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
Kato
Tadafumi
T
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. kato@brain.riken.jp.
D000328:Adult; D044466:Asian People / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D012559:Schizophrenia / Q000235:genetics