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

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.

• Authors: 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
• Journal: Schizophrenia research (Schizophr Res) Vol. 112 Issue 1-3 Pg. 72-9 (Jul 2009) ISSN: 1573-2509 [Electronic] Netherlands
• PMID: 19406621 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Methionine
• Valine

Topics

• Adult
• Brain-Derived Neurotrophic Factor (genetics)
• Case-Control Studies
• Female
• Gene Frequency
• Genotype
• Humans
• Japan (ethnology)
• Linkage Disequilibrium
• Male
• Methionine (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Schizophrenia (genetics)
• Valine (genetics)
• Young Adult