BDNF gene is a risk factor for schizophrenia in a Scottish population

Maria De Lurdes Neves-Pereira, John Kwok Shing Cheung, Alireza Pasdar, Feng Zhang, Gerome Daniel Breen, P. Yates, Caroline Margaret Crombie, N. Walker, David Malcolm St Clair

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Abstract

Schizophrenia is a severe psychiatric disease with a strong genetic component. Brain-derived neurotrophic factor ( BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar ( BP) disorders. The present study has examined two polymorphisms in linkage disequilibrium in the BDNF gene, which have been variously reported as associated with schizophrenia and BP. In our study, 321 probands with a primary diagnosis of schizophrenia or schizoaffective disorder, and 263 with a diagnosis of bipolar affective disorder, were examined together with 350 controls drawn from the same geographical region of Scotland. The val66met single-nucleotide polymorphism ( SNP) showed significant ( P = 0.005) association for valine ( allele G) with schizophrenia but not bipolar disorder. Haplotype analysis of val/ met SNP and a dinucleotide repeat polymorphism in the putative promoter region revealed highly significant ( P<1 x 10(-8)) under-representation of the methionine or met-1 haplotype in the schizophrenic but not the BP population. We conclude that, although the val66met polymorphism has been reported to alter gene function, the risk may depend upon the haplotypic background on which the val/ met variant is carried.

Original languageEnglish
Pages (from-to)208-212
Number of pages4
JournalMolecular Psychiatry
Volume10
DOIs
Publication statusPublished - Jan 2005

Keywords

  • bipolar disorder
  • schizophrenia
  • association study
  • genetics
  • risk
  • haplotype analysis
  • NEUROTROPHIC FACTOR GENE
  • DINUCLEOTIDE REPEAT POLYMORPHISM
  • GENOME SCAN METAANALYSIS
  • FAMILY-BASED ASSOCIATION
  • BIPOLAR-DISORDER
  • LINKAGE DISEQUILIBRIUM
  • CANDIDATE GENES
  • MESSENGER-RNA
  • 6P22.3 GENE
  • BRAIN

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