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

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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

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Brain-Derived Neurotrophic Factor
Meta-Analysis
Schizophrenia
Population
Single Nucleotide Polymorphism
Linkage Disequilibrium
Alleles
HapMap Project
Bipolar Disorder
Gene Frequency
Microsatellite Repeats
Case-Control Studies

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Kawashima, Kunihiro ; Ikeda, Masashi ; Kishi, Taro ; Kitajima, Tsuyoshi ; Yamanouchi, Yoshio ; Kinoshita, Yoko ; Okochi, Tomo ; Aleksic, Branko ; Tomita, Makoto ; Okada, Takeya ; Kunugi, Hiroshi ; Inada, Toshiya ; Ozaki, Norio ; Iwata, Nakao. / BDNF is not associated with schizophrenia : Data from a Japanese population study and meta-analysis. In: Schizophrenia Research. 2009 ; Vol. 112, No. 1-3. pp. 72-79.
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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.",
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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, vol. 112, no. 1-3, pp. 72-79. https://doi.org/10.1016/j.schres.2009.03.040

BDNF is not associated with schizophrenia : Data from a Japanese population study and meta-analysis. / Kawashima, Kunihiro; Ikeda, Masashi; Kishi, Taro; Kitajima, Tsuyoshi; Yamanouchi, Yoshio; Kinoshita, Yoko; Okochi, Tomo; Aleksic, Branko; Tomita, Makoto; Okada, Takeya; Kunugi, Hiroshi; Inada, Toshiya; Ozaki, Norio; Iwata, Nakao.

In: Schizophrenia Research, Vol. 112, No. 1-3, 01.07.2009, p. 72-79.

Research output: Contribution to journalArticle

TY - JOUR

T1 - BDNF is not associated with schizophrenia

T2 - Data from a Japanese population study and meta-analysis

AU - Kawashima, Kunihiro

AU - Ikeda, Masashi

AU - Kishi, Taro

AU - Kitajima, Tsuyoshi

AU - Yamanouchi, Yoshio

AU - Kinoshita, Yoko

AU - Okochi, Tomo

AU - Aleksic, Branko

AU - Tomita, Makoto

AU - Okada, Takeya

AU - Kunugi, Hiroshi

AU - Inada, Toshiya

AU - Ozaki, Norio

AU - Iwata, Nakao

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

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