Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control sample of over 3000 individuals from the UK

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuronal survival, proliferation and plasticity. Three family-based studies have shown association of the common Valine (Val) allele of the Val66Met polymorphism of the BDNF gene with susceptibility to bipolar disorder. AIMS: To replicate this finding. METHOD: We genotyped the Val66Met polymorphism in our UK White bipolar case-control sample (n=3062). RESULTS: We found no overall evidence of allele or genotype association. However, we found association with disease status in the subset of 131 individuals that had experienced rapid cycling at some time (P=0.004). We found a similar association on re-analysis of our previously reported family-based association sample (P <0.03, one-tailed test). CONCLUSIONS: Variation at the Val66Met polymorphism of BDNF does not play a major role in influencing susceptibility to bipolar disorder as a whole, but is associated with susceptibility to the rapid-cycling subset of the disorder.