Association analysis of HSP90B1 with bipolar disorder
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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.
KeywordsBipolar disorder HSP90B1/GRP94/gp96 Association study Evi12 Endoplasmic reticulum stress Retrovirus
This research was supported by a grant for Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, a Grant-in-Aid from Japanese Ministry of Health and Labor, and a Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors declare no conflict of interest.
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