Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder - Case-control study 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 Val 66Met 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 Val 66 Met 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. Declaration of interest N.C. and M.J.O. are consultants to GlaxoSmith Kline and have received grant funding and honoraria from GlaxoSmith Kline, AstraZeneca and Eli Lilly. M.C. O'D., A.H.Y., L.J. and G.K. have received honoraria from GlaxoSmith Kline, AstraZeneca and Eli Lilly G.K. has received grant funding from Janssen. Funding detailed in Acknowledgements.