Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder

Am J Hum Genet. 2003 Aug;73(2):370-6. doi: 10.1086/377003. Epub 2003 Jun 27.


We evaluated a possible association between the brain-derived neurotrophic factor (BDNF) gene and susceptibility to obsessive-compulsive disorder (OCD) by genotyping a number of single-nucleotide polymorphisms (SNPs) and one microsatellite marker from the extended BDNF locus in 164 triads with OCD. Extensive background linkage disequilibrium was observed at this locus. Single-locus transmission-distortion tests revealed significant evidence of association with the disease for all the BDNF gene markers tested, including a Val66Met variation affecting the sequence of the proBDNF protein. Analysis of multi-SNP haplotypes provided similar results. Haplotype transmission comparisons in this and previous studies point to a functionally distinct BDNF haplotype uniquely marked by the rare Met66 allele, which is undertransmitted and likely confers a protective effect in OCD and other psychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics*
  • Child
  • Exons
  • Female
  • Genetic Variation*
  • Genotype
  • Haplotypes
  • Humans
  • Introns
  • Linkage Disequilibrium
  • Male
  • Microsatellite Repeats
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Precursors / genetics


  • Brain-Derived Neurotrophic Factor
  • Protein Precursors
  • brain-derived neurotrophic factor precursor