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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)72-79
Number of pages8
JournalSchizophrenia Research
Volume112
Issue number1-3
DOIs
Publication statusPublished - 01-07-2009

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

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