BDNF is not associated with schizophrenia: data from a Japanese population study and meta-analysis.
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.
Kawashima
Kunihiro
K
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Ikeda
Masashi
M
Kishi
Taro
T
Kitajima
Tsuyoshi
T
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Okochi
Tomo
T
Aleksic
Branko
B
Tomita
Makoto
M
Okada
Takeya
T
Kunugi
Hiroshi
H
Inada
Toshiya
T
Ozaki
Norio
N
Iwata
Nakao
N
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
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine