BDNF is not associated with schizophrenia: Data from a Japanese population study and meta-analysis

Kunihiro Kawashima, Masashi Ikeda, Taro Kishi, Tsuyoshi Kitajima, Yoshio Yamanouchi, Yoko Kinoshita, Tomo Okochi, Branko Aleksic, Makoto Tomita, Takeya Okada, Hiroshi Kunugi, Toshiya Inada, Norio Ozaki, Nakao Iwata

研究成果: Article

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A variety of evidence suggests brain-derived neurotrophic factor (BDNF) as a candidate gene for schizophrenia, and several genetic studies have shown a significant association between the disease and certain SNPs within BDNF (specifically, Val66Met and C270T). According to a recent study, the functional microsatellite marker BDNF-LCPR (BDNF-linked complex polymorphic region), which affects the expression level of BDNF, is associated with bipolar disorder. The goals of our current study were to 1) evaluate the quality of HapMap-based linkage disequilibrium (LD) tagging of BDNF-LCPR, 2) examine whether these tagging SNPs are associated with schizophrenia in a Japanese population, and 3) conduct a meta-analysis of the two most extensively studied polymorphisms: Val66Met and C270T. We genotyped eight tagging SNPs, including Val66Met and C270T. Our LD evaluation showed that BDNF-LCPR could be represented by these tagging SNPs in controls (with 73.5% allelic coverage). However, the functional A1 allele was not captured due to its low minor allele frequency (2.2%). In a case-control study (1117 schizophrenics and 1102 controls), no association was found in single-marker or multimarker analysis. Moreover, in a meta-analysis, the Val66Met polymorphism was not associated with schizophrenia, whereas C270T showed a trend for association in a fixed model (p = 0.036), but not in a random model (p = 0.053). From these findings, we conclude that if BDNF is indeed associated with schizophrenia, the A1 allele in BDNF-LCPR would be the most promising candidate. Further LD evaluation, as well as an association study in which BDNF-LCPR is genotyped directly, would be required for a more conclusive result.

元の言語English
ページ(範囲)72-79
ページ数8
ジャーナルSchizophrenia Research
112
発行部数1-3
DOI
出版物ステータスPublished - 01-07-2009

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

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    Kawashima, K., Ikeda, M., Kishi, T., Kitajima, T., Yamanouchi, Y., Kinoshita, Y., Okochi, T., Aleksic, B., Tomita, M., Okada, T., Kunugi, H., Inada, T., Ozaki, N., & Iwata, N. (2009). BDNF is not associated with schizophrenia: Data from a Japanese population study and meta-analysis. Schizophrenia Research, 112(1-3), 72-79. https://doi.org/10.1016/j.schres.2009.03.040