title: 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.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kawashima
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kitajima
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Tomo
authors.initials: T
authors.lastname: Okochi
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Makoto
authors.initials: M
authors.lastname: Tomita
authors.forename: Takeya
authors.initials: T
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine