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Reply to "Lack of support for a genetic association of the XBP1 promoter polymorphism with bipolar disorder in probands of European origin"

Nature Genetics volume 36, pages 784–785 (2004)Cite this article

In reply

We previously concluded that an impaired XBP1 loop is a genetic risk factor for bipolar disorder1 based on multiple lines of evidence: (i) downregulation of XBP1 and HSPA5 in twins discordant for bipolar disorder; (ii) reduced response of XBP1 and HSPA5 to endoplasmic reticulum (ER) stress in cells lines established from individuals with bipolar disorder; (iii) identification of a functional polymorphism, −116C→ G, in the promoter of XBP1; (iv) association of this polymorphism with bipolar disorder in Japanese case-control samples; (v) confirmation of this association in a small number of European American trios; and (vi) improvement of the functional impairment due to the −116G allele by valproate. The findings of Cichon and colleagues, by genotyping enough samples of European origin to test our finding, indicate that the fifth finding was type I error. We agree that the association in Japanese individuals should be tested in larger number of independent samples.

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References

  1. Kakiuchi, C. et al. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat. Genet. 35, 171–175 (2003).

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Acknowledgements

Data and biomaterials of the NIMH pedigrees were collected in four projects that participated in the NIMH Bipolar Disorder Genetics Initiative. From 1991–1998, the Principal Investigators andCo-Investigators were as follows: J. Nurnberger, M. Miller and E. Bowman (Indiana University); T. Reich, A. Goate and J. Rice (Washington University); J.R. DePaulo Jr., S. Simpson and C. Stine (Johns Hopkins University); and E. Gershon, D. Kazuba and E. Maxwell (NIMH Intramural Research Program).

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Authors and Affiliations

  1. Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, 351-0198, Saitama, Japan

    Chihiro Kakiuchi & Tadafumi Kato

  2. Department of Psychiatry, Teikyo University School of Medicine, Itabashi, 173-8605, Tokyo, Japan

    Shinichiro Nanko

  3. Department of Mental Disorder Research, National Institute of Neuroscience, Kodaira, 187-8502, Tokyo, Japan

    Hiroshi Kunugi

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  1. Chihiro Kakiuchi
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  2. Shinichiro Nanko
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  3. Hiroshi Kunugi
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  4. Tadafumi Kato
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Correspondence to Tadafumi Kato.

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Kakiuchi, C., Nanko, S., Kunugi, H. et al. Reply to "Lack of support for a genetic association of the XBP1 promoter polymorphism with bipolar disorder in probands of European origin". Nat Genet 36, 784–785 (2004). https://doi.org/10.1038/ng0804-784

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