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

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.